File - Working Toward Zero HAIs

Transcription

THE DIAGNOSIS OF PERIPROSTHETIC JOINT
INFECTIONS OF THE HIP AND KNEE
GUIDELINE AND EVIDENCE REPORT
Adopted by the American Academy of Orthopaedic Surgeons
Board of Directors
June 18, 2010
Disclaimer
This Clinical Practice Guideline was developed by an AAOS physician volunteer Work
Group based on a systematic review of the current scientific and clinical information and
accepted approaches to treatment and/or diagnosis. This Clinical Practice Guideline is not
intended to be a fixed protocol, as some patients may require more or less treatment or
different means of diagnosis. Clinical patients may not necessarily be the same as those
found in a clinical trial. Patient care and treatment should always be based on a
clinician’s independent medical judgment, given the individual patient’s clinical
circumstances.
Disclosure Requirement
In accordance with AAOS policy, all individuals whose names appear as authors or
contributors to Clinical Practice Guideline filed a disclosure statement as part of the
submission process. All panel members provided full disclosure of potential conflicts of
interest prior to voting on the recommendations contained within this Clinical Practice
Guidelines.
Funding Source
This Clinical Practice Guideline was funded exclusively by the American Academy of
Orthopaedic Surgeons who received no funding from outside commercial sources to
support the development of this document.
FDA Clearance
Some drugs or medical devices referenced or described in this Clinical Practice Guideline
may not have been cleared by the Food and Drug Administration (FDA) or may have
been cleared for a specific use only. The FDA has stated that it is the responsibility of the
physician to determine the FDA clearance status of each drug or device he or she wishes
to use in clinical practice.
Copyright
All rights reserved. No part of this Clinical Practice Guideline may be reproduced, stored
in a retrieval system, or transmitted, in any form, or by any means, electronic,
mechanical, photocopying, recording, or otherwise, without prior written permission
from the AAOS.
Published 2010 by the American Academy of Orthopaedic Surgeons
6300 North River Road
Rosemont, IL 60018
First Edition
Copyright 2010
by the American Academy of Orthopaedic Surgeons
ii
AAOS Clinical Practice Guidelines Unit
v0.1 03.25.10
Summary of Recommendations
The following is a summary of the recommendations in the AAOS’ clinical practice
guideline, The Diagnosis of Periprosthetic Joint Infections of the Hip and Knee. This
summary does not contain rationales that explain how and why these recommendations
were developed nor does it contain the evidence supporting these recommendations. All
readers of this summary are strongly encouraged to consult the full guideline and
evidence report for this information. We are confident that those who read the full
guideline and evidence report will note that the recommendations were developed using
systematic evidence-based processes designed to combat bias, enhance transparency, and
promote reproducibility.
This summary of recommendations is not intended to stand alone. Clinical decisions
should be made in light of all circumstances presented by the patient. Procedures
applicable to the individual patient rely on mutual communication between patient,
physician, and other healthcare practitioners.
1. In the absence of reliable evidence about risk stratification of patients with a
potential periprosthetic joint infection, it is the opinion of the work group that
testing strategies be planned according to whether there is a higher or lower
probability that a patient has a hip or knee periprosthetic infection.
Strength of Recommendation: Consensus
Note: Please see page 17 of this document for a definition of “higher and lower
probability”.
2. We recommend erythrocyte sedimentation rate and C-reactive protein testing
for patients assessed for periprosthetic joint infection.
Strength of Recommendation: Strong
3. We recommend joint aspiration of patients being assessed for periprosthetic
knee infections who have abnormal erythrocyte sedimentation rate AND/OR Creactive protein results. We recommend that the aspirated fluid be sent for
microbiologic culture, synovial fluid white blood cell count and differential.
iii
v0.1 03.25.10
4. We recommend a selective approach to aspiration of the hip based on the
patient’s probability of periprosthetic joint infection and the results of the
erythrocyte sedimentation rate (ESR) AND C-reactive protein (CRP). We
recommend that the aspirated fluid be sent for microbiologic culture, synovial
fluid white blood cell count and differential.
Selection of Patients for Hip Aspiration
Probability of
Infection
ESR and CRP
Results
Planned Reoperation
Status
Recommended Test
Higher
+ + or + −
Planned or not planned
Aspiration
Lower
+ + or + −
Planned
Aspiration or Frozen Section
Lower
++
Not planned
Aspiration
Lower
+−
Not planned
Please see Recommendation 6
Higher or Lower
−−
No further testing
Key for ESR and CRP results
+ + = ESR and CRP test results are abnormal
+ − = either ESR or CRP test result is abnormal
− − = ESR and CRP test results are normal
5. We suggest a repeat hip aspiration when there is a discrepancy between the
probability of periprosthetic joint infection and the initial aspiration culture
result.
Strength of Recommendation: Moderate
6. In the absence of reliable evidence, it is the opinion of the work group that
patients judged to be at lower probability for periprostheic hip infection and
without planned reoperation who have abnormal erythrocyte sedimentation rates
OR abnormal C-reactive protein levels be re-evaluated within three months. We
are unable to recommend specific diagnostic tests at the time of this follow-up.
7. In the absence of reliable evidence, it is the opinion of the work group that a
repeat knee aspiration be performed when there is a discrepancy between the
probability of periprosthetic joint infection and the initial aspiration culture
result.
8. We suggest patients be off of antibiotics for a minimum of 2 weeks prior to
obtaining intra-articular culture.
iv
v0.1 03.25.10
9. Nuclear imaging (Labeled leukocyte imaging combined with bone or bone
marrow imaging, FDG-PET imaging, Gallium imaging, or labeled leukocyte
imaging) is an option in patients in whom diagnosis of periprosthetic joint
infection has not been established and are not scheduled for reoperation.
Strength of Recommendation: Weak
10. We are unable to recommend for or against computed tomography (CT) or
magnetic resonance imaging (MRI) as a diagnostic test for periprosthetic joint
infection.
Strength of Recommendation: Inconclusive
11. We recommend against the use of intraoperative Gram stain to rule out
periprosthetic joint infection.
12. We recommend the use of frozen sections of peri-implant tissues in patients
who are undergoing reoperation for whom the diagnosis of periprosthetic joint
infection has not been established or excluded.
13. We recommend that multiple cultures be obtained at the time of reoperation in
patients being assessed for periprosthetic joint infection.
14. We recommend against initiating antibiotic treatment in patients with suspected
periprosthetic joint infection until after cultures from the joint have been
obtained.
15. We suggest that prophylactic preoperative antibiotics not be withheld in patients
at lower probability for periprosthetic joint infection and those with an
established diagnosis of periprosthetic joint infection who are undergoing
reoperation.
v
v0.1 03.25.10
Work Group
Craig Della Valle MD, Chair
Rush University Medical Center
1611 W Harrison St # 300
Chicago, IL 60612-4861
Guidelines and Technology Oversight
Chair:
William C. Watters III MD
6624 Fannin #2600
Houston, TX 77030
Javad Parvizi, MD, Vice-Chair
Rothman Institute
925 Chestnut St - 5th Fl
Philadelphia, PA 19107
Evidence Based Practice Committee Chair:
Michael Keith, MD
2500 Metro Health Drive
Cleveland, OH 44109-1900
Thomas W Bauer, MD PhD
Cleveland Clinic Foundation
Department of Pathology
9500 Euclid Ave Desk L25
Cleveland, OH 44195
AAOS Staff:
Charles M. Turkelson, PhD
Director of Research and Scientific Affairs
6300 N River Road
Rosemont, IL 60018
Paul E DiCesare, MD
UC Davis Medical Center
Department of Orthopaedic Surgery
4860 Y St Ste 3800
Sacramento, CA 95817
Janet L. Wies MPH
AAOS Clinical Practice Guideline Mgr
Patrick Sluka MPH
AAOS Research Analyst
Richard Parker Evans, MD
University of Arkansas for Medical Sciences
Department of Orthopedics
4301 W Markham, #531
Little Rock, AR 72205
Kristin Hitchcock, MSI
AAOS Medical Librarian
Special Acknowledgements
Sara Anderson MPH
Kevin Boyer
Laura Raymond, MA
John Segreti, MD
600 S Paulina St. Ste 143
Chicago, Il 60612
Mark Spangehl, MD
Mayo Clinic
5777 East Mayo Blvd
Phoenix, AZ 85054
vi
v0.1 03.25.10
Peer Review
Participation in the AAOS peer review process does not constitute an endorsement
of this guideline by the participating organization.
The following organizations participated in peer review of this clinical practice guideline
and gave explicit consent to be listed in this document:
American Association of Hip and Knee Surgeons
European Bone and Joint Infection Society
Knee Society
Musculoskeletal Infection Society
Society of Nuclear Medicine
vii
v0.1 03.25.10
Table of Contents
SUMMARY OF RECOMMENDATIONS ..............................................................III
WORK GROUP .................................................................................................. VI
PEER REVIEW .................................................................................................. VII
TABLE OF CONTENTS ................................................................................... VIII
LIST OF FIGURES ............................................................................................ XII
LIST OF TABLES............................................................................................. XIII
I.
INTRODUCTION ...........................................................................................1
Overview ....................................................................................................................................................... 1
Goals and Rationale ..................................................................................................................................... 1
Intended Users .............................................................................................................................................. 1
Patient Population ........................................................................................................................................ 2
Etiology.......................................................................................................................................................... 2
Incidence ....................................................................................................................................................... 2
Burden of Disease ......................................................................................................................................... 2
Risk Factors .................................................................................................................................................. 2
Emotional and Physical Impact................................................................................................................... 2
Potential Benefits and Harms...................................................................................................................... 2
II.
METHODS.....................................................................................................3
Formulating Preliminary Recommendations............................................................................................. 3
Study Selection Criteria ............................................................................................................................... 3
Inclusion of studies with mixed patient populations.................................................................................. 4
Best Available Evidence............................................................................................................................ 4
Literature Searches ...................................................................................................................................... 4
Data Extraction............................................................................................................................................. 5
viii
v0.1 03.25.10
Judging the Quality of Evidence ................................................................................................................. 5
Diagnostic Studies ..................................................................................................................................... 5
Prognostic Studies ..................................................................................................................................... 7
Defining the Strength of the Recommendations ........................................................................................ 7
Consensus Development............................................................................................................................... 8
Statistical Methods ....................................................................................................................................... 9
Peer Review................................................................................................................................................... 9
Public Commentary.................................................................................................................................... 10
The AAOS Guideline Approval Process................................................................................................... 10
Revision Plans ............................................................................................................................................. 10
Guideline Dissemination Plans .................................................................................................................. 10
III.
ALGORITHMS .........................................................................................12
IV.
RECOMMENDATIONS AND SUPPORTING DATA ...............................15
Recommendation 1 ..................................................................................................................................... 15
Summary of Evidence.............................................................................................................................. 18
Excluded Articles..................................................................................................................................... 21
Study Quality........................................................................................................................................... 34
Study Results ........................................................................................................................................... 40
Recommendation 2 ..................................................................................................................................... 44
Study Quality........................................................................................................................................... 51
Study Results ........................................................................................................................................... 56
Recommendation 3 ..................................................................................................................................... 74
Study Quality........................................................................................................................................... 77
Study Results ........................................................................................................................................... 78
Recommendation 4 ..................................................................................................................................... 85
Study Quality........................................................................................................................................... 90
Study Results ........................................................................................................................................... 92
Recommendation 5 ................................................................................................................................... 101
Excluded Articles................................................................................................................................... 102
Study Quality......................................................................................................................................... 103
Study Results ......................................................................................................................................... 103
Recommendation 6 ................................................................................................................................... 104
ix
v0.1 03.25.10
Recommendation 7 ................................................................................................................................... 106
Recommendation 8 ................................................................................................................................... 107
Study Quality......................................................................................................................................... 109
Study Results ......................................................................................................................................... 109
Recommendation 9 ................................................................................................................................... 110
Summary of Evidence............................................................................................................................ 113
Study Quality......................................................................................................................................... 123
Study Results ......................................................................................................................................... 128
Recommendation 10 ................................................................................................................................. 146
Study Quality......................................................................................................................................... 148
Study Results ......................................................................................................................................... 150
Recommendation 11 ................................................................................................................................. 153
Study Quality......................................................................................................................................... 155
Study Results ......................................................................................................................................... 156
Recommendation 12 ................................................................................................................................. 159
Study Quality......................................................................................................................................... 163
Study Results ......................................................................................................................................... 165
Recommendation 13 ................................................................................................................................. 171
Study Quality......................................................................................................................................... 176
Study Results ......................................................................................................................................... 178
Recommendation 14 ................................................................................................................................. 189
Study Quality......................................................................................................................................... 191
Study Results ......................................................................................................................................... 192
Recommendation 15 ................................................................................................................................. 193
Study Quality......................................................................................................................................... 197
Study Results ......................................................................................................................................... 199
Future Research ....................................................................................................................................... 201
V.
APPENDIXES............................................................................................203
Appendix I................................................................................................................................................. 204
Work Group........................................................................................................................................... 204
x
v0.1 03.25.10
Appendix II ............................................................................................................................................... 205
AAOS Bodies That Approved This Clinical Practice Guideline ........................................................... 205
Documentation of Approval .................................................................................................................. 206
Appendix III.............................................................................................................................................. 207
Study Attrition Flowchart ...................................................................................................................... 207
Appendix IV.............................................................................................................................................. 208
Literature Searches ................................................................................................................................ 208
Appendix V ............................................................................................................................................... 211
Data Extraction Elements ...................................................................................................................... 211
Appendix VI.............................................................................................................................................. 212
Judging the Quality of Diagnostic Studies............................................................................................. 212
Judging the Quality of Prognostic Studies............................................................................................. 213
Judging the Quality of Treatment Studies ............................................................................................. 213
Appendix VII ............................................................................................................................................ 214
Form for Assigning Strength of Recommendation (Interventions) ....................................................... 214
Appendix VIII........................................................................................................................................... 216
Voting by the Nominal Group Technique ............................................................................................. 216
Opinion-Based Recommendations ........................................................................................................ 216
Appendix IX.............................................................................................................................................. 219
Structured Peer Review Form................................................................................................................ 219
Appendix X ............................................................................................................................................... 222
Peer Review Panel ................................................................................................................................. 222
Public Commentary ............................................................................................................................... 223
Appendix XI.............................................................................................................................................. 224
Interpreting the Forest Plots................................................................................................................... 224
Appendix XII ............................................................................................................................................ 225
Conflict of Interest................................................................................................................................. 225
Appendix XIII........................................................................................................................................... 227
References ............................................................................................................................................. 227
Articles Excluded from the Systematic Review(s) ................................................................................ 237
xi
v0.1 03.25.10
List of Figures
Algorithm for Patients with Higher Probability of Hip or Knee Periprosthetic Joint
Infection ................................................................................................................ 12
Algorithm for Patients with Lower Probability of Periprosthetic Knee Infection............ 13
Algorithm for Patients with Lower Probability of Periprosthetic Hip Infection with
Planned Reoperation ............................................................................................. 14
Algorithm for Patients with Lower Probability of Periprosthetic Hip Infection without
Planned Reoperation ............................................................................................. 14
ESR Meta-analysis Results - Likelihood Ratios............................................................... 56
CRP Results - Likelihood Ratios ...................................................................................... 57
ESR and CRP - Likelihood Ratios.................................................................................... 57
Radiography Results - Likelihood Ratios ......................................................................... 58
White Blood Cell Count Results - Likelihood Ratios....................................................... 58
Hip Aspiration Cultures Results - Meta-Analysis ............................................................ 92
Synovial Fluid WBC Count Results - Likelihood Ratios (Hip and Knee) ....................... 93
Neutrophil Percentage Results – Likelihood Ratios (Hip and Knee) ............................... 93
Technetium-labeled-Leukocyte Imaging Results – Likelihood Ratios .......................... 128
Indium-labeled-Leukocyte Imaging Results - Likelihood Ratios................................... 129
Combined Leukocyte/Bone Imaging Results – Likelihood Ratios................................. 129
Combined Leukocyte/Bone Marrow Imaging Results - Likelihood Ratios ................... 130
FDG-PET Imaging Results - Likelihood Ratios............................................................. 130
Technetium-99m Bone Imaging Results - Likelihood Ratios ........................................ 131
Other Nuclear Imaging Results - Likelihood Ratios....................................................... 132
CT Imaging Results - Likelihood Ratios ........................................................................ 150
Gram Stain Results - Likelihood Ratios ......................................................................... 156
Frozen Section Meta-Analysis – Threshold of 10 PMN in 5 Fields............................... 165
Frozen Section Meta-Analysis – Threshold of 5 PMN/HPF .......................................... 165
Frozen Section Results - Likelihood Ratios – Mixed Thresholds .................................. 166
Intraoperative Cultures Results - Threshold of 1 vs. 2 Positive Cultures....................... 178
Intraoperative Cultures Results - Tissue or Swab or Fluid ............................................. 178
xii
v0.1 03.25.10
List of Tables
Reference Standard Used in Included Diagnostic Studies.................................................. 6
Strength of recommendation descriptions .......................................................................... 8
AAOS Guideline Language ................................................................................................ 8
Interpreting Likelihood Ratios............................................................................................ 9
Results of Prognostic Studies - Hip .................................................................................. 18
Results of Prognostic Studies - Knee................................................................................ 19
Summary of Evidence – Diagnostic or Prevalence Studies.............................................. 20
Excluded Articles - Recommendation 1 ........................................................................... 21
Quality of Diagnostic Studies ........................................................................................... 34
Quality of Prognostic Studies ........................................................................................... 35
Risk Factors - Quality of Joint Registries ......................................................................... 38
Risk Factors - Quality of Randomized Trials ................................................................... 39
Pain as a Predictor of Periprosthetic Infection.................................................................. 40
Warmth, Erythema, Swelling as Predictors of Periprosthetic Infection ........................... 40
Early Implant Failure as a Predictor of Periprosthetic Infection ...................................... 41
Sinus Tract as a Predictor of Periprosthetic Infection ...................................................... 41
Prevalence of Periprosthetic Infection among Patients with Bacteremia ......................... 41
Prevalence of Periprosthetic Infection among Patients with Metachronous Periprosthetic
Infection ................................................................................................................ 42
Anticoagulation RCT ........................................................................................................ 42
Use of Drains RCTs .......................................................................................................... 43
Radiography and Serology Summary of Evidence........................................................... 46
Radiography and Serology - Quality ................................................................................ 51
Erythrocyte Sedimentation Rate Results .......................................................................... 59
C-Reactive Protein Results ............................................................................................... 62
ESR and CRP Results ....................................................................................................... 65
Radiography Results ......................................................................................................... 67
White Blood Cell Count Results....................................................................................... 70
Knee Aspiration Summary of Evidence ........................................................................... 75
Knee Aspiration - Quality................................................................................................. 77
Aspiration Culture - Knee................................................................................................. 78
Synovial Fluid White Blood Cell Count........................................................................... 79
Synovial Fluid Neutrophil Percentage .............................................................................. 82
Aspiration Summary of Evidence..................................................................................... 86
Aspiration - Quality .......................................................................................................... 90
Aspiration Culture - Hip ................................................................................................... 94
Synovial Fluid White Blood Cell Count........................................................................... 96
Synovial Fluid Neutrophil Percentage .............................................................................. 99
Excluded Articles - Recommendation 5 ......................................................................... 102
Repeat Aspiration - Quality ............................................................................................ 103
Repeat Aspiration Results............................................................................................... 103
xiii
v0.1 03.25.10
Excluded Article - Recommendation 7........................................................................... 106
Preoperative Antibiotic Therapy - Quality ..................................................................... 109
Preoperative Antibiotics and False-Negative Cultures ................................................... 109
Nuclear Imaging Summary of Evidence......................................................................... 113
Nuclear Imaging - Quality .............................................................................................. 123
Technetium-99m-labeled-Leukocyte Imaging................................................................ 133
Indium-111-labeled-Leukocyte Imaging ........................................................................ 135
Combined Leukocyte/Bone Imaging .............................................................................. 136
Combined Leukocyte/Bone Marrow Imaging ................................................................ 138
Gallium-67 Imaging........................................................................................................ 141
FDG-PET Imaging.......................................................................................................... 142
Technetium-99m Bone Imaging ..................................................................................... 144
Other Nuclear Imaging tests ........................................................................................... 145
CT and MRI Summary of Evidence ............................................................................... 146
Excluded Articles - Recommendation 10 ....................................................................... 147
Study Quality - CT.......................................................................................................... 148
CT Imaging ..................................................................................................................... 151
Gram Stain Summary of Evidence ................................................................................. 153
Gram Stain - Quality....................................................................................................... 155
Intraoperative Gram Stain Results .................................................................................. 157
Frozen Section Summary of Evidence............................................................................ 160
Frozen Section - Quality ................................................................................................. 163
Frozen Section Results.................................................................................................... 167
Summary of Evidence..................................................................................................... 171
Intraoperative Cultures - Quality .................................................................................... 176
Overall and number of cultures results ........................................................................... 179
Tissue vs. Swab vs. Fluid................................................................................................ 186
Excluded Articles - Recommendation14 ........................................................................ 190
Preoperative Antibiotic Therapy - Quality ..................................................................... 191
Preoperative Antibiotics - Diagnostic Study Quality...................................................... 197
Preoperative Antibiotics - Randomized Trial Quality .................................................... 198
Preoperative Antibiotics - Joint Registry Quality........................................................... 198
Relative Risk of Infection - Placebo vs. Preoperative Antibiotics.................................. 199
Registry Data – Hazard Ratio of Revision due to Infection ........................................... 200
xiv
v0.1 03.25.10
I. INTRODUCTION
OVERVIEW
This clinical practice guideline is based on a systematic review of published studies on
the diagnosis of periprosthetic joint infections of the hip and knee. In addition to
providing practice recommendations, this guideline also highlights gaps in the literature
and areas that require future research.
This guideline is intended to be used by all appropriately trained surgeons and all
qualified physicians evaluating patients for periprosthetic joint infections of the hip and
knee. It is also intended to serve as an information resource for decision makers and
developers of practice guidelines and recommendations.
GOALS AND RATIONALE
The purpose of this clinical practice guideline is to help improve treatment based on the
current best evidence. Current evidence-based practice (EBP) standards demand that
physicians use the best available evidence in their clinical decision making. This clinical
practice guideline was developed following systematic review of the available literature
regarding the diagnosis of periprosthetic infections of the hip and the knee. The
systematic review detailed herein was conducted between October 2008 and September
2009 and demonstrates where there is good evidence, where evidence is lacking, and
what topics future research must target in order to improve the diagnosis of periprosthetic
joint infections of the hip and knee. AAOS staff and the physician work group
systematically reviewed the available literature and subsequently wrote the following
recommendations based on a rigorous, standardized process.
Musculoskeletal care is provided in many different settings by many different providers.
We created this guideline as an educational tool to guide qualified physicians through a
series of diagnostic decisions in an effort to improve the quality and efficiency of care.
This guideline should not be construed as including all proper methods of care or
excluding methods of care reasonably directed to obtaining the same results. The ultimate
judgment regarding any specific procedure or treatment must be made in light of all
circumstances presented by the patient and the needs and resources particular to the
locality or institution. Further, the scope of the guideline does not include information on
laboratory techniques or tissue sampling techniques beyond the evidence presented to
support Recommendations 13 and 14. It is assumed that the well qualified physician will
use his/her best judgement, considering the individual patient circumstances as well as
the available resources, when addressing these issues.
INTENDED USERS
This guideline is intended to be used by orthopaedic surgeons and all qualified physicians
managing the diagnosis of periprosthetic joint infections of the hip and knee. Typically,
orthopaedic surgeons will have completed medical training, a qualified residency in
orthopaedic surgery, and some may have completed additional sub-specialty training. It is
also intended to serve as an information resource for professional healthcare practitioners
and developers of practice guidelines and recommendations.
1
v0.1 03.25.10
PATIENT POPULATION
This document addresses the diagnosis of periprosthetic joint infections in patients who
have undergone arthroplasty of the hip or knee This guideline is not intended for patients
with superficial infections.
ETIOLOGY
Periprosthetic joint infection can be caused by entry of organisms into the wound during
surgery, hematogenous spread, recurrence of sepsis in a previously infected joint, or
contiguous spread of infection from a local source.22
INCIDENCE
The incidence of periprosthetic joint infection after primary hip or knee arthroplasty is
over 2% among the Medicare population.56, 76 The incidence of periprosthetic infection is
higher after revision arthroplasty than after primary arthroplasty in both joints.64, 82
BURDEN OF DISEASE
Periprosthetic joint infection requires significant resources to diagnose and treat.
Infection is a common cause of revision arthroplasty, with 15% of revision total hip
arthroplasties and 25% of revision total knee arthroplasties being due to infection.12, 13
RISK FACTORS
Risk factors identified and supported by the evidence include prior infection of the joint
(knee), superficial surgical site infection (hip and knee), obesity (hip), extended operative
time (>2.5 hours, hip and knee) and immunosuppression (knee). The work group also
discusses additional risk factors based on consensus in Recommendation 1.
EMOTIONAL AND PHYSICAL IMPACT
Periprosthetic joint infection is a serious complication of total joint replacement resulting
in significant morbidity, including pain, loss of function, and potential removal of the
prosthesis.
POTENTIAL BENEFITS AND HARMS
There is the possibility of harm resulting from diagnostic tests, including the possibility
of the introduction of bacteria into the joint during an aspiration and patient pain and/or
discomfort while undergoing the procedure. Therefore, discussion of available diagnostic
procedures applicable to the individual patient rely on mutual communication between
the patient and physician, weighing the potential risks and benefits for that patient.
2
v0.1 03.25.10
II. METHODS
This section describes the methods used to prepare this guideline and systematic review,
including search strategies used to identify literature, criteria for selecting eligible
articles, determining the strength of the evidence, data extraction, methods of statistical
analysis, and the review and approval of the guideline. The methods used to perform this
systematic review were employed to minimize bias in the selection and analysis of the
available evidence.17, 69 This is vital to the development of reliable, transparent, and
accurate clinical recommendations for diagnosing periprosthetic joint infections of the
hip and knee.
The AAOS Diagnosis of Periprosthetic Joint Infections of the Hip and Knee physician
work group prepared this guideline and systematic review with the assistance of the
AAOS Clinical Practice Guidelines Unit in the Department of Research and Scientific
Affairs at the AAOS (Appendix I).
To develop this guideline, the work group held an introductory meeting to develop the
scope of the guideline on October 17 and 18, 2008. Upon completion of the systematic
review, the work group met again on September 12 and 13, 2009 to write and vote on the
final recommendations and rationales for each recommendation. The resulting draft
guidelines were then peer-reviewed, subsequently sent for public commentary, and then
sequentially approved by the AAOS Evidence Based Practice Committee, AAOS
Guidelines and Technology Oversight Committee, AAOS Council on Research, Quality
Assessment, and Technology, and the AAOS Board of Directors (see Appendix II for a
description of the AAOS bodies involved in the approval process)
FORMULATING PRELIMINARY RECOMMENDATIONS
The work group began work on this guideline by constructing a set of preliminary
recommendations. These recommendations specify [what] should be done in [whom],
[when], [where], and [how often or how long]. They function as questions for the
systematic review, not as final recommendations or conclusions. Preliminary
recommendations are almost always modified on the basis of the results of the systematic
review. Once established, these a priori preliminary recommendations cannot be
modified until the final work group meeting, they must be addressed by the systematic
review, and the relevant review results must be presented in the final guideline.
STUDY SELECTION CRITERIA
We developed a priori article inclusion criteria for our review. These criteria are our
“rules of evidence” and articles that do not meet them are, for the purposes of this
guideline, not evidence.
To be included in our systematic reviews (and hence, in this guideline) an article had to
be a report of a study that:
•
Addressed the value of tests for diagnosis of periprosthetic joint infection in
the hip and knee.
3
v0.1 03.25.10
•
Was written in English and published in or after 1970. For MRI, CT and PET
only studies published after 2000 were included. For other nuclear imaging
modalities, only studies published after 1975 were considered.
•
Was not an abstract, unpublished study report, letter, case report, historical
article, editorial, tutorial, traditional review or commentary.
•
Was published in the peer-reviewed literature.
•
Was not a cadaveric, animal, or an in vitro study.
•
Included 25 or more patients per study arm.
•
Reported sufficient data to construct a 2 x 2 table.
•
Was of the highest level of available evidence (best available evidence),
assuming that there were two or more studies of that higher level. Hip and
knee studies were considered separately. For example, if there were two Level
II studies of the hip and two Level II studies of the knee that addressed the
recommendation Level III and IV studies were not included.
•
Was not evaluating a test in a cohort where the infected prosthesis had already
been removed (no more than 10% of cohort or data from these patients
reported separately).
INCLUSION OF STUDIES WITH MIXED PATIENT POPULATIONS
The work group specified a priori to the literature search that data would be stratified by
joint but that mixed studies could be accepted and reported as such.
BEST AVAILABLE EVIDENCE
When examining primary studies, we analyzed the best available evidence regardless of
study design. We first considered the randomized controlled trials identified by the search
strategy. In the absence of two or more RCTs, we sequentially searched for prospective
controlled trials, prospective comparative studies, retrospective comparative studies, and
prospective case-series studies. Only studies of the highest level of available evidence
were included, assuming that there were 2 or more studies of that higher level. For
example, if there were two Level II studies that addressed the recommendation, Level III
and IV studies were not included.
LITERATURE SEARCHES
We attempted to make our searches for articles comprehensive. Using comprehensive
literature searches ensures that the evidence we considered for this guideline is not biased
for (or against) any particular point of view.
We searched for articles published from January 1970 to August 10, 2009. Strategies for
searching electronic databases were constructed by a Medical Librarian to identify
4
v0.1 03.25.10
relevant clinical studies. We searched four electronic databases; PubMed, EMBASE,
CINAHL, and The Cochrane Central Register of Controlled Trials.
All searches of electronic databases were supplemented with manual screening of the
bibliographies of all retrieved publications. We also searched the bibliographies of recent
systematic reviews and other review articles for potentially relevant citations. Finally,
work group members provided a list of potentially relevant studies that were not
identified by our searches. All articles identified were subject to the study selection
criteria listed above.
The study attrition diagram in Appendix III provides details about the inclusion and
exclusion of the studies considered for this guideline. The search strategies used to
identify these studies are provided in Appendix IV.
DATA EXTRACTION
Data elements extracted from studies were defined in consultation with the physician
work group. One analyst completed data extraction for all studies. The elements extracted
are shown in Appendix V. Evidence tables were constructed to summarize the best
evidence pertaining to each preliminary recommendation. Disagreements about the
accuracy of extracted data were resolved by discussion and consulting the physician work
group.
The work group specified a priori to the literature search that data would be stratified by
joint but that mixed studies could be accepted and reported as such. When studies did not
separate the data by joint, we could not report them separately. If a study with mixed
joints reported the data for each joint we reported them as such. If a study reported
mixed joints but had fewer than 25 patients per joint, only the mixed data was reported.
JUDGING THE QUALITY OF EVIDENCE
Determining the quality of the included evidence is vitally important when preparing any
evidence-based work product. Doing so conveys the amount of confidence one can have
in any study’s results. One has more confidence in high quality evidence than in low
quality evidence.
Assigning a level of evidence on the basis of study design plus other quality
characteristics ties the levels of evidence we report more closely to quality than levels of
evidence based only on study design. Because we tie quality to levels of evidence, we are
able to characterize the confidence one can have in their results. Accordingly, we
characterize the confidence one can have in Level I evidence as high, the confidence one
can have in Level II and III evidence as moderate, and the confidence one can have in
Level IV and V evidence as low. Similarly, throughout the guideline we refer to Level I
evidence as reliable, Level II and III evidence as moderately reliable, and Level IV and V
evidence as not reliable.
DIAGNOSTIC STUDIES
We used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) instrument
to identify potential bias and assess variability and the quality of reporting in studies
5
v0.1 03.25.10
reporting the effectiveness of diagnostic techniques.109 Studies without any indication of
bias are categorized as Level I studies. Studies with a known bias are downgraded to
Level IV or Level III (for a bias for which we have or have not found published evidence
that this bias affects diagnostic results, respectively). Studies with more than one bias are
downgraded to Level V. Those studies that do not sufficiently report their methods for a
potential bias are downgraded to Level II since we are unable to determine if the bias did
or did not bias the results of the study (see Appendix VI).
Although the definition of a reference standard varies in the periprosthetic joint infection
literature, intraoperative cultures have been used most often as the reference standard in
interpreting the results of a diagnostic test, as indicated in Table 1. Accordingly, when
possible we also used intraoperative cultures as a reference standard when computing
measures of test performance.
Table 1. Reference Standard Used in Included Diagnostic Studies
Reference Standard
(Infection defined as positive results on following test(s))
Intraoperative cultures
Intraoperative cultures and histology
Histology
At least 2 of intraoperative cultures, purulence, and histology
Intraoperative cultures or histology
Number of Studies
18
7
4
4
3
Open wound or sinus communicating with the joint OR systemic
infection with pain in the hip and purulent fluid within the joint
OR positive result on at least 3 tests (ESR, CRP, joint aspiration,
intraoperative frozen section, and intraoperative culture)
3
Histology or purulence or sinus tract communicating with the
prosthesis
2
Intraoperative cultures or purulence
Aspiration or intraoperative cultures
2
1
At least 2 of intraoperative cultures, purulence, and histology; or
2 positive cultures
1
Histology and gross operative findings
Intraoperative cultures or histology or purulence
Intraoperative cultures or histology or deep abscess
1
1
1
Cultures or purulence or histology or sinus tract communicating
with the prosthesis
1
Correlation between intraoperative cultures and histology; the
appearance of the tissue intraoperatively; and the clinical course
1
Intraoperative cultures and gross sepsis
1
At least 3 of CRP, ESR, aspiration culture, intraoperative
purulence, intraoperative culture
1
6
v0.1 03.25.10
Reference Standard
(Infection defined as positive results on following test(s))
Number of Studies
Abscess or sinus tract communicating with the joint space OR
aspiration culture OR ≥2 intraoperative cultures OR 1 culture and
purulence or histology OR purulence and histology
1
PROGNOSTIC STUDIES
In studies investigating the effect of a characteristic on the outcome of disease, we
assessed quality using a two-step process. Any study that investigated a prospectively
enrolled cohort of patients and utilized regression analysis was initially categorized as a
Level I study. A study that used regression analysis in a retrospectively enrolled cohort of
patients was categorized as a Level II study. A case-control study that used regression
analysis was categorized as a Level III study. We next assessed the outcome (dependent
variable) for each prognostic factor (independent variable) using a quality questionnaire
and, when quality standards were not met, we downgraded the level of evidence by one
level (Appendix VI).
DEFINING THE STRENGTH OF THE RECOMMENDATIONS
Judging the quality of evidence is only a stepping stone towards arriving at the strength
of a guideline recommendation. Unlike Levels of Evidence (which apply only to a given
result at a given follow-up time in a given study) strength of recommendation takes into
account the quality, quantity, and applicability of the available evidence. Strength also
takes into account the trade-off between the benefits and harms of a treatment or
diagnostic procedure, and the magnitude of a treatment’s effect.
Strength of recommendation expresses the degree of confidence one can have in a
recommendation. As such, the strength expresses how possible it is that a
recommendation will be overturned by future evidence. It is very difficult for future
evidence to overturn a recommendation that is based on many high quality randomized
controlled trials that show a large effect. It is much more likely that future evidence will
overturn recommendations derived from a few small case series. Consequently,
recommendations based on the former kind of evidence are given a high strength of
recommendation and recommendations based on the latter kind of evidence are given a
low strength.
To develop the strength of a recommendation, AAOS staff first assigned a preliminary
strength for each recommendation that took only the quality and quantity of the available
evidence into account (see Table 2). Work group members then modified the preliminary
strength using the ‘Form for Assigning Strength of Recommendation (Interventions)’
shown in Appendix VII.
7
v0.1 03.25.10
Table 2. Strength of recommendation descriptions
Strength
Overall
Quality of
Evidence
Strong
Good
Moderate
Fair
Weak
Poor
Inconclusive
None or
Conflicting
Consensus
No
Evidence
Description of Evidence
Level I evidence from more than one study with consistent
findings for recommending for or against the intervention
or diagnostic.
Level II or III evidence from more than one study with
consistent findings, or Level I evidence from a single study
for recommending for or against the intervention or
diagnostic.
Level IV or V evidence from more than one study with
consistent findings, or Level II or III evidence from a single
study for recommending for against the intervention or
diagnostic.
The evidence is insufficient or conflicting and does not
allow a recommendation for or against the intervention or
diagnostic.
There is no supporting evidence. In the absence of reliable
evidence, the work group is making a recommendation
based on their clinical opinion considering the known
harms and benefits associated with the treatment.
Each recommendation was written using language that accounts for the final strength of
the recommendation. This language, and the corresponding strength, is shown in Table 3.
Table 3. AAOS Guideline Language
Strength of
Recommendation
Strong
Moderate
Weak
Inconclusive
Guideline Language
We recommend
We suggest
option
We are unable to recommend for or against
In the absence of reliable evidence, it is the
Consensus
opinion of this work group
CONSENSUS DEVELOPMENT
The recommendations and their strength were voted on using a structured voting
technique known as the nominal group technique.71 We present details of this technique
in Appendix VIII. Voting on guideline recommendations was conducted using a secret
ballot and workgroup members were blinded to the responses of other members. If
disagreement between workgroup members was significant, there was further discussion
8
v0.1 03.25.10
to see whether the disagreement(s) could be resolved. Up to three rounds of voting were
held to attempt to resolve disagreements. If disagreements were not resolved following
three voting rounds, no recommendation was adopted. Lack of agreement is a reason that
the strength for some recommendations are labeled as “Inconclusive.”
STATISTICAL METHODS
Likelihood ratios, sensitivity, specificity and 95% confidence intervals were used to
determine the accuracy of diagnostic modalities based on two by two diagnostic
contingency tables extracted from the included studies. When possible, prognostic factors
were analyzed according to sensitivity and specificity as well.80 Likelihood ratios (LR)
indicate the magnitude of the change in probability of disease due to a given test result.
For example, a positive likelihood ratio of 10 indicates that a positive test result is 10
times more common in patients with disease than in patients without disease. Likelihood
ratios are interpreted according to previously published values, as seen in Table 4.42
Likelihood ratios, sensitivity, specificity and 95% confidence intervals were calculated in
STATA 10.0 (StataCorp LP, College Station, Texas). For meta-analysis of diagnostic
tests, we used the bivariate random effects model.38, 39, 89 Meta-analyses were conducted
only if there were at least four studies for a given diagnostic test. When a meta-analysis
indicated between-study heterogeneity (I2 >50%) and thresholds for a positive test result
varied between studies, we included the threshold as a covariate in the model to
determine whether the heterogeneity could be explained by the variation in thresholds.
Table 4. Interpreting Likelihood Ratios
Positive
Likelihood Ratio
Negative
Likelihood Ratio
Interpretation
>10
<0.1
Large and conclusive change in probability
5-10
0.1-0.2
Moderate change in probability
2-5
0.2-0.5
1-2
0.5-1
Small (but sometimes important) change in
probability
Small (and rarely important) change in
probability
PEER REVIEW
The draft of this guideline and evidence report was peer reviewed by an expert, outside
advisory panel that was nominated a priori by the physician work group prior to the
development of the guideline. The physician members of the AAOS Guidelines and
Technology Oversight Committee and the Evidence Based Practice Committee also
provided peer review of the draft document. Peer review was accomplished using a
structured peer review form (see Appendix IX). The draft guideline was sent to a total of
11 reviewers and 10 of these members returned reviews (see Appendix X) within the
designated time frame. The disposition of all non-editorial peer review comments was
documented and accompanied this guideline through the public commentary and the
AAOS guideline approval process.
9
v0.1 03.25.10
PUBLIC COMMENTARY
After modifying the draft in response to peer review, the guideline was subjected to a
thirty day period of “Public Commentary.” Commentators consist of members of the
AAOS Board of Directors (BOD), members of the Council on Research, Quality
Assessment, and Technology (CORQAT), members of the Board of Councilors (BOC),
and members of the Board of Specialty Societies (BOS). Based on these bodies, up to
185 commentators had the opportunity to provide input into this guideline development
process. Of these, 10 members of the BOC and 7 members of the BOS requested that we
send them the document during the period of public comment. In addition, the Executive
Directors of the Hip Society and the Orthopaedic Trauma Association each requested that
we send additional drafts to two of their members. A member of the IDSA also requested
the opportunity to provide comment on the draft and was forwarded all materials. One of
these 22 members returned public comments. The single peer reviewer who did not return
his comments during the time frame for peer review returned his comments during the
period of public comment. We responded to both of these revewers’ comments. (see
Appendix X).
THE AAOS GUIDELINE APPROVAL PROCESS
Following public commentary, the draft was again modified by the AAOS Clinical
Practice Guidelines Unit and work group members. This final guideline draft was
approved by the AAOS Guidelines Oversight Committee, the AAOS Evidence Based
Practice Committee, the AAOS Council on Research, Quality Assessment, and
Technology, and the AAOS Board of Directors. Descriptions of these bodies are provided
in Appendix II.
REVISION PLANS
This guideline represents a cross-sectional view of current diagnosis and may become
outdated as new evidence becomes available. The AAOS may revise this guideline in
accordance with new evidence, changing practice, rapidly emerging treatment options, or
new technology. This guideline will be updated or withdrawn in five years in accordance
with the standards of the National Guideline Clearinghouse.
GUIDELINE DISSEMINATION PLANS
The primary purpose of the present document is to provide interested readers with full
documentation about not only our recommendations, but also about how we arrived at
those recommendations. This document is also posted on the AAOS website at
http://www.aaos.org/research/guidelines/guide.asp.
Shorter versions of the guideline are available in other venues. Publication of most
guidelines is announced by an Academy press release, articles authored by the work
group and AAOS staff and published in the Journal of the American Academy of
Orthopaedic Surgeons and the Journal of Bone & Joint Surgery, and articles published in
AAOS Now. Most guidelines are also distributed at the AAOS Annual Meeting in various
venues such as on Academy Row and at Committee Scientific Exhibits.
10
v0.1 03.25.10
Selected guidelines are disseminated by webinar, an Online Module for the Orthopeadic
Knowledge Online website, Radio Media Tours, Media Briefings, and by distributing
them at relevant Continuing Medical Education (CME) courses and at the AAOS
Resource Center.
Other dissemination efforts outside of the AAOS will include submitting the guideline to
the National Guideline Clearinghouse and distributing the guideline at other medical
specialty societies’ meetings.
11
v0.1 03.25.10
III. ALGORITHMS
This section presents algorithms illustrating the recommendations of the guideline.
Readers are encouraged to use them when reading the document.
Figure 1. Algorithm for Patients with Higher Probability of Hip or Knee
Periprosthetic Joint Infection
1
Patient at higher probability of
periprosthetic joint infection of the hip
or knee being assessed for infection
3
2
ESR/
CRP:
either
positive?
Yes
4
Aspirate
joint
5
Both Cell
count/differential
AND Culture
positive?
Infection
Likely
Yes
No
6
7
Either cell
count/differential
OR culture
positive?
Repeat
aspiration:
positive?
Yes
Yes
9
Frozen section
AND/OR
Intra-operative
synovial fluid
white blood cell
count/differential:
positive?
No
8
No
Is surgery
planned?
No
Yes
No
10
Nuclear
imaging:
positive?
12
Yes
11
Yes
Infection
Likely
No
No
Infection
Unlikely
Box 7: Perform repeat aspiration when there is a discrepancy between the probability of infection
and the initial aspiration culture result
Box 9: Perform frozen section when the diagnosis has not been established at the time of surgery;
synovial fluid white blood cell count and differential may also be obtained intra-operatively
Box 10: Nuclear imaging modalities: Labeled leukocyte imaging combined with bone or bone
marrow imaging, FDG-PET imaging, Gallium imaging, or labeled leukocyte imaging
12
v0.1 03.25.10
Figure 2. Algorithm for Patients with Lower Probability of Periprosthetic Knee
Infection
1
2
Patient at lower probability of
periprosthetic knee infection being
assessed for infection
4
ESR/
CRP:
either
positive?
3
Yes
Aspirate
joint
5
Both Cell
count/differential
AND Culture
positive?
Infection
Likely
Yes
No
6
Either cell
count/differential
OR culture
positive?
7
Yes
Repeat
aspiration:
positive?
Yes
9
No
No
8
Is surgery
planned?
No
Yes
No
10
11
Observe and
Re-evaluate
at 3 months
Frozen section
AND/OR
Intra-operative
synovial fluid
white blood cell
count/differential:
positive?
Yes
No
Infection
Unlikely
and the initial aspiration culture result
Box 9: Perform frozen section when the diagnosis has not been established at the time of surgery;
synovial fluid white blood cell count and differential may also be obtained intra-operatively
13
v0.1 03.25.10
Figure 3. Algorithm for Patients with Lower Probability of Periprosthetic Hip
Infection with Planned Reoperation
1
Patient with planned reoperation
at lower probability of periprosthetic
hip infection being assessed for
infection
2
3
ESR/
CRP:
either
positive?
Yes
Aspiration (preor intraoperative)
AND/OR
Frozen section:
positive?
No
5
4
Infection
Likely
Yes
No
Infection
Unlikely
Box 3: Perform aspiration (pre- or intraoperative) in all patients including synovial fluid white
blood cell count and differential; perform frozen section when the diagnosis has not been
established at the time of surgery.
Figure 4. Algorithm for Patients with Lower Probability of Periprosthetic Hip
Infection without Planned Reoperation
1
Patient without planned reoperation
at lower probability of periprosthetic hip
infection being assessed for infection
2
ESR/
CRP:
both
positive?
4
3
Yes
Aspirate
joint
No
7
Yes
Observe and
Re-evaluate
at 3 months
8
Either cell
count/differential
OR culture
positive?
No
5
Yes
Infection
Likely
No
6
Either
ESR or
CRP
positive?
5
Both Cell
count/differential
AND Culture
positive?
No
9
Yes
Repeat
aspiration:
positive?
Yes
No
Infection
Unlikely
and the initial aspiration culture result.
14
v0.1 03.25.10
IV. RECOMMENDATIONS AND SUPPORTING DATA
RECOMMENDATION 1
In the absence of reliable evidence about risk stratification of patients with a potential
periprosthetic joint infection, it is the opinion of the work group that testing strategies be
planned according to whether there is a higher or lower probability that a patient has a hip
or knee periprosthetic infection.
Rationale
The diagnosis of periprosthetic infection can be difficult to make and many tests are
available to the clinician. Identification of a periprosthetic joint infection is important, as
subsequent treatment is fundamentally different between cases that have a septic as
opposed to an aseptic mode of failure. Specifically, a missed diagnosis of infection can
lead to a high rate of subsequent failure if specific treatment for the infection is not
considered.
Pre-test probability is weighted heavily in the performance of any diagnostic test. Thus
the identification of a patient as having a higher or lower probability of periprosthetic
joint infection, when initiating the diagnostic evaluation is important. Further, a
determination of how likely or unlikely a diagnosis is, based on patient symptoms, risk
factors, co-morbidities and the physical examination is typically an integral part of the
evaluation that guides clinical decisions. Based on these factors, despite the paucity of
high-level data that supports the specific identification of such factors as they relate to the
probability of periprosthetic joint infection, it is important to outline factors that can
assist the clinician in identifying patients who have a higher probability of periprosthetic
infection and thus warrant a more extensive diagnostic evaluation. Similarly, in patients
who are deemed to have a lower probability of periprosthetic infection, a less vigorous
evaluation may be warranted. Clinicians oftentimes make such assessments of probability
routinely in their practice that leads to more prudent selections among testing modalities
that are based on specific individual patient characteristics. This routine assessment is of
limited cost and low morbidity to the patient.
While the list compiled by the work group is not meant to be exhaustive, several risk
factors were identified as supported by the available evidence as associated with the
presence of periprosthetic joint infection as outlined below. Additional factors, not
supported by the available literature, but unanimously agreed upon by the work group as
additional risk factors to consider were also identified. Finally, several potential risk
factors were identified that the literature did not support as being associated with a
greater probability of periprosthetic infection including smoking status, obesity for
patients who have undergone total knee arthroplasty, the use of drains, and
immunocompromising states for patients who have undergone a total hip arthroplasty.
Analysis of the literature revealed that prolonged post-operative wound drainage and
15
v0.1 03.25.10
hematoma formation appeared to increase the likelihood of periprosthetic joint infection
on univariate analysis; however, this was not confirmed by multivariate analysis.
The work group proposes the following table for stratifying patients into higher or lower
probability of infection:
One or more symptoms, AND at least one or more:
1) risk factor;* OR
Higher
Probability of 2) physical exam finding; OR
3) early implant loosening/osteolysis (as detected by xInfection
ray)
Pain or joint stiffness only and none of the following:
1) risk factors;* OR
Lower
Probability of 2) physical exam findings; OR
3) early implant loosening/osteolysis (as detected by xInfection
ray)
*risk factor supported by evidence or expert opinion
Factors for Risk Stratification
Symptoms
1. Pain in
the
replaced
joint
2. Stiffness
in the
replaced
joint
Risk Factors
Risk Factors Supported
Supported by
by Evidence
Consensus
1. Prior infection of the
1. Any recent (<1yr.)
joint (knee)
bacteremia or
2. Superficial surgical
candidemia
site infection (hip and 2. Metachronous
knee)
prosthetic joint
3. Obesity (hip)
infection
4. Extended operative
3. Skin disorders
time (>2.5 hours, hip
(psoriasis, chronic
and knee)
cellulitis,
5. Immunosuppression*
lymphedema,
(knee)
chronic venous
stasis, skin ulcers)
4. IV drug use
5. Recent (<3 yrs.)
MRSA infection
or colonization
6. Active infection at
other site
Physical
Exam
Other
Findings
1. Warmth,
1. Early (<5
effusion,
yrs.)
redness,
implant
swelling
loosening
2. Sinus
or
tract
osteolysis
associated
(as
with the
detected by
joint
x-ray)
Factors not supported as a risk by evidence
1. Smoking
2. Obesity (knee)
3. Use of drains
4. Hematoma or use of anticoagulation (INR>2 or low molecular weight heparins)
16
v0.1 03.25.10
5. Immunosuppression* (hip)
*The systematic review considered the following states as indicative of
immunosuppression: HIV, diabetes, hepatitis, chemotherapy or other suppressive
medication such as antimonoclonal antibodies (medications specified in search:
prednisone, infliximab, adalimumab, methotrexate, etanercept), autoimmune diseases
(lupus, rheumatoid arthritis, ankylosing spondylitis, Reiter’s syndrome, psoriatic
arthropathy), inflammatory arthritis, renal disease (chronic renal failure, dialysis), liver
failure, malnourishment, sickle cell disease, hemophilia, solid organ transplant
Supporting Evidence
We included four Level II, two Level III, one Level IV and one Level V prognostic
studies of hip patients (or mixed hip and knee patients with a majority of hip patients).6,
24, 41, 50, 61, 86, 98, 112
We included the lower level studies if they addressed a specific risk
factor that had not been addressed by multiple studies of higher quality. The results of
each study may not be directly comparable with the other studies because the study
authors included different covariates in each model. The results are summarized in Table
5.
We included five Level II, two Level III and one Level IV prognostic studies of knee
patients (or mixed hip and knee patients with a majority of knee patients). 1, 10, 25, 41, 43, 79,
92, 112
We included the lower level studies if they addressed a specific risk factor that had
not been addressed by multiple studies of higher quality. The results of each study may
not be directly comparable with the other studies because the study authors included
different covariates in each model. The results are summarized in Table 6.
We also included thirteen randomized trials investigating the use of drains and one
randomized trial investigating the use of anticoagulation.7, 16, 18, 29, 36, 40, 44, 45, 51, 52, 74, 77, 91,
107
The anticoagulation trial and ten of the drain trials had no periprosthetic infections in
either arm. None of the other three drain trials found a statistically significant difference
in infection rates between groups (see Table 20).
We included seven diagnostic studies for this recommendation. Two studies of other
diagnostic modalities reported data on patients with pain;63, 106 two reported on warmth,
redness, or swelling;63, 102 one reported on sinus tracts;63 and one reported on early
implant failure.57 Two prevalence studies addressed metachronous periprosthetic joint
infection (PJI),62, 72 and one prevalence study addressed recent septicemia.70 With the
exception of the study which reported on early implant failure, the data from these studies
are of low quality and therefore not reliable. The results are summarized in Table 7.
There were no included studies that addressed stiffness, prior MRSA or VRE infection,
skin disorders, IV drug use, or planned revision surgery. We did not include studies on
the prevalence of infection after all revision surgeries because these studies included
patients with revision surgeries planned due to infection. The inclusion of these patients
limits the applicability of these studies.
17
v0.1 03.25.10
Author
N
Level of
Evidence
Extended Operative Time
Prior Infection of the Joint
Immunosuppression
Obesity
Smoking
Other SSI
Use of Drains
Other Variable(s)
( e.g., Age, Sex, etc.)
Wound Drainage or
Hematoma or Anticoagulation
SUMMARY OF EVIDENCE
Table 5. Results of Prognostic Studies - Hip
Huotari
5614
II
x
●
x
○
x
x
x
x
I
Lubbeke
2495
II
x
x
x
x
●
x
x
x
I
Smabrekke 28020 II
x
●
x
x
x
x
x
x
I
Wymenga
2547
II
○
○
x
○
x
x
●
x
I
Dowsey
1207
III
x
x
x
I
●
x
x
x
x
Pulido
9245
III
○
○
x
○
●
x
○
x
I
Berbari
924
IV
○
*
○
○
○
x
●
○
I
Khan
1767
V
x
x
x
x
x
○
x
x
x
* ● = statistically significant, ○ = not significant, x = not studied, I = included as covariate or
matching variable, but data not reported * = extended operative time was studied but the results
were reported by the authors as part of a composite measure.
18
v0.1 03.25.10
Author
N
Level of
Evidence
Extended Operative Time
Prior Infection of the Joint
Immunosuppression
Obesity
Smoking
Other SSI
Use of Drains
Other Variable(s)
( e.g., Age, Sex, etc.)
Wound Drainage or
Hematoma or Anticoagulation
Table 6. Results of Prognostic Studies - Knee
Amin
82
II
x
x
x
x
○
x
x
x
I
Bordini
9735
II
x
x
x
x
○
x
x
x
I
Huotari
4217
II
x
●
x
○
x
x
x
x
I
Jamsen
primary:
38338
II
revision:
2061
x°
x
●
●
x
x
x°
x
I
Wymenga 345
II
○
○
x
○
x
x
●
x
I
Dowsey
1214
III
x
x
x
●
●
○
x
Z
I
Saleh
97
III
x
x
x
x
x
x
●
x
I
Peersman
349
IV
x
x
x
●
●
●
x
x
I
* ● = statistically significant, ○ = not significant, x = not studied, I = included as covariate or
matching variable, but data not reported, Z = statistically significant protection
° Jamsen study grouped postoperative complications together, including wound hematoma and
wound infections; a postoperative complication was a statistically significant risk factor
19
v0.1 03.25.10
Table 7. Summary of Evidence – Diagnostic or Prevalence Studies
Clinical
Indication
Early Implant
Loosening
Pain
Warmth,
swelling
Sinus Tract
Level of
Evidence
Prevalence of Infection
among Patients with
Indication
Positive
Likelihood Ratio
(95% CI)
Negative
Likelihood Ratio
(95% CI)
I
24%
15-51%
2.1
(1.36, 3.25)
1 – 1.18
0.53
(0.29, 0.96)
-
IV-V
IV
71-100%
2.3 – 2.88
0.82 – 0.92
IV
100%
-
0.86
(0.77, 0.96)
Recent
V
45% hematogenous
n/a
Septicemia
Metachronous
V
15-19%
n/a
PJI
*Prevalence based on two studies if range presented, one if a single number
20
v0.1 03.25.10
EXCLUDED ARTICLES
Table 8. Excluded Articles - Recommendation 1
Author
Abudu, et al.
2002
Title
The outcome of perioperative wound infection after total hip and knee arthroplasty
Reason for Exclusion
Not best available
evidence
Abuzakuk, et al.
2007
Autotransfusion drains in total knee replacement. Are they alternatives to homologous
transfusion?
Does not address
recommendation
Ahlberg, et al.
1981
Secondary operations after knee joint replacement
Not best available
evidence
Ainscow, et al.
1984
The risk of haematogenous infection in total joint replacements
Not best available
evidence
Amin, et al.
2006
Does obesity influence the clinical outcome at five years following total knee replacement
for osteoarthritis?
Not best available
evidence
Amin, et al.
2008
A prospective randomised controlled trial of autologous retransfusion in total knee
replacement
Does not address
recommendation
Andrew, et al.
2008
Obesity in total hip replacement
Not best available
evidence
Andrews, et al.
1981
Deep infection after total hip replacement
Not best available
evidence
Asensio, et al.
2005
Preoperative low molecular weight heparin as venous thromboembolism prophylaxis in
patients at risk for prosthetic infection after knee arthroplasty
Not best available
evidence
Bahebeck, et al.
2009
Implant orthopaedic surgery in HIV asymptomatic carriers: Management and early
outcome
<25 arthroplasty
patients per group
Bedi, et al.
1997
An audit of early hospital readmission after primary knee joint replacement
<25 patients/arm
Bengtson, et al.
1991
The infected knee arthroplasty. A 6-year follow-up of 357 cases
Not best available
evidence
21
v0.1 03.25.10
Table 8. Excluded Articles (Continued)
Author
Title
Beyer, et al.
1991
Primary total knee arthroplasty in patients with psoriasis
Not best available
evidence
Bohm, et al.
1998
Is there a future for hinged prostheses in primary total knee arthroplasty? A 20-year
survivorship analysis of the Blauth prosthesis
Not best available
evidence
Bong, et al.
2004
Stiffness after total knee arthroplasty
Narrative review,
bibliography screened
Bongartz, et al.
2008
Incidence and risk factors of prosthetic joint infection after total hip or knee replacement in
patients with rheumatoid arthritis
Not best available
evidence
Bosch, et al.
1980
An analysis of 119 loosenings in total hip endoprostheses
Insufficient Data
Bourne, et al.
1994
Pain in the thigh following total hip replacement with a porous-coated anatomic prosthesis
for osteoarthrosis. A five-year follow-up study
Does not address
recommendation
Brander, et al.
2003
Predicting Total Knee Replacement Pain: A Prospective, Observational Study
Does not address
recommendation
Byrne, et al.
2007
Outcome following deep wound contamination in cemented arthroplasty
Not best available
evidence
Cameron,
1993
Knee effusion after total knee replacement
Narrative review,
Carlsson,
1981
351 total hip replacements according to Charnley. A review of complications and function
Not best available
evidence
Chan, et al.
1996
Obesity and quality of life after primary hip arthroplasty
Does not address
recommendation
Charnley,
1972
Postoperative infection after total hip replacement with special reference to air
contamination in the operating room
Not best available
evidence
22
v0.1 03.25.10
Author
Title
Cherney, et al.
1983
Total hip replacement in the previously septic hip
No comparison group
Chesney, et al.
2008
Infection after knee arthroplasty a prospective study of 1509 cases
Not best available
evidence
Choong, et al.
2007
Risk factors associated with acute hip prosthetic joint infections and outcome of treatment
with a rifampinbased regimen
Not best available
evidence
Clements, et al.
2007
Risk stratification for surgical site infections in Australia: evaluation of the US National
Nosocomial Infection Surveillance risk index
Not relevant - not
specific to pji
Dennis,
2004
Evaluation of painful total knee arthroplasty
Narrative review,
Deshmukh, et al.
2002
Does body weight influence outcome after total knee arthroplasty? A 1-year analysis
Not relevant - not
specific to pji
Dowsey, et al.
2008
Early outcomes and complications following joint arthroplasty in obese patients: a review
of the published reports
Systematic review,
Dowsey, et al.
2008
Obesity is a major risk factor for prosthetic infection after primary hip arthroplasty
Not best available
evidence
Drancourt, et al.
1997
Psoriasis is a risk factor for hip-prosthesis infection
<25 patients
Drinkwater, et al.
1995
Optimal timing of wound drain removal following total joint arthroplasty
Does not address
recommendation
Duffy, et al.
2005
Evaluation of patients with pain following total hip replacement
Narrative review,
Duffy, et al.
2006
Evaluation of patients with pain following total hip replacement
Narrative review,
23
v0.1 03.25.10
Author
Title
Ehrenkranz,
1981
Surgical wound infection occurrence in clean operations; risk stratification for interhospital
comparisons
Not relevant - not
specific to pji
Espehaug, et al.
1997
Patient-related risk factors for early revision of total hip replacements. A population
register-based case-control study of 674 revised hips
Not best available
evidence
Fan, et al.
2008
Infection in primary total knee replacement
Insufficient Data
Fernandez, et al.
1997
Risk infection factors in the total hip replacement
Fitzgerald, et al.
1977
Deep wound sepsis following total hip arthroplasty
Foldes, et al.
1992
Ultrasonography after hip arthroplasty
<25 patients/arm
Foran, et al.
2004
The outcome of total knee arthroplasty in obese patients
Not best available
evidence
Foran, et al.
2004
Total knee arthroplasty in obese patients: a comparison with a matched control group
Not best available
evidence
Gaine, et al.
2000
Wound infection in hip and knee arthroplasty
Not relevant - not
specific to pji
Galat, et al.
2008
Early return to surgery for evacuation of a postoperative hematoma after primary total
knee arthroplasty
Not best available
evidence
Galat, et al.
2009
Surgical treatment of early wound complications following primary total knee arthroplasty
Not relevant - not
specific to pji
Garibaldi, et al.
1991
Risk factors for postoperative infection
Not relevant - not
specific to pji
Not relevant - no
relevant risk factors
investigated
Not best available
evidence
24
v0.1 03.25.10
Author
Title
Gonzalez, et al.
2004
The failed total knee arthroplasty: evaluation and etiology
Narrative review,
Gordon, et al.
1990
Risk factors for wound infections after total knee arthroplasty
Not best available
evidence
Grant, et al.
2008
Two-year outcomes in primary THA in obese male veterans administration medical center
patients
Not relevant - not
specific to pji
Greene, et al.
1991
Preoperative nutritional status of total joint patients. Relationship to postoperative wound
complications
Not best available
evidence
Hamilton, et al.
2008
Deep infection in total hip arthroplasty
Not best available
evidence
Horberg, et al.
2006
Surgical outcomes in human immunodeficiency virus-infected patients in the era of highly
active antiretroviral therapy
Not relevant - not
specific to pji
Horne, et al.
2008
The influence of steroid injections on the incidence of infection following total knee
arthroplasty
Not relevant - not
specific to pji
Ibrahim, et al.
2005
No influence of body mass index on early outcome following total hip arthroplasty
Not best available
evidence
Ilstrup, et al.
1973
Factors influencing the results in 2,012 total hip arthroplasties
Insufficient Data
Jaberi, et al.
2008
Procrastination of wound drainage and malnutrition affect the outcome of joint
arthroplasty
Does not address
recommendation
Jacobsen, et al.
1980
Prophylactic coverage of dental patients with artificial joints: a retrospective analysis of
thirty-three infections in hip prostheses
Does not address
recommendation
Jacobson, et al.
1986
Dental treatment and late prosthetic joint infections
Does not address
recommendation
25
v0.1 03.25.10
Author
Title
Jain, et al.
2005
Comorbidities increase complication rates in patients having arthroplasty
Not relevant - not
specific to pji
James, et al.
1982
Total hip revision arthroplasty: does sepsis influence the results?
Narrative review,
Jensen, et al.
1982
Nutrition in orthopaedic surgery
Insufficient Data
Jerry, et al.
1988
Old sepsis prior to total knee arthroplasty
No comparison group
Jibodh, et al.
2004
In-hospital outcome and resource use in hip arthroplasty: Influence of body mass
Not best available
evidence
Jiganti, et al.
1993
A comparison of the perioperative morbidity in total joint arthroplasty in the obese and
nonobese patient
Not best available
evidence
Johnson, et al.
1986
The outcome of infected arthroplasty of the knee
Not best available
evidence
Jones, et al.
1979
GUEPAR knee arthroplasty results and late complications
Not best available
evidence
Jupiter, et al.
1981
Total hip arthroplasty in the treatment of adult hips with current or quiescent sepsis
No comparison group
Kaspar, et al.
2005
Infection in hip arthroplasty after previous injection of steroid
Not best available
evidence
Kessler, et al.
2003
Influence of operation duration on perioperative morbidity in revision total hip arthroplasty
Not relevant - not
specific to pji
Khuri, et al.
1995
The National Veterans Administration Surgical Risk Study: risk adjustment for the
comparative assessment of the quality of surgical care
Not relevant - not
specific to pji
26
v0.1 03.25.10
Author
Title
Kim,
1991
Total arthroplasty of the hip after childhood sepsis
No comparison group
Kim, et al.
2003
Total hip arthroplasty in adult patients who had childhood infection of the hip
No comparison group
Kim, et al.
2006
Clinical impact of obesity on stability following revision total hip arthroplasty
Insufficient Data
Kim, et al.
2004
Stiffness after total knee arthroplasty. Prevalence of the complication and outcomes of
revision
Does not address
recommendation
Knobben, et al.
2006
Intraoperative contamination influences wound discharge and periprosthetic infection
Not best available
evidence
Knutson, et al.
1986
Survival of knee arthroplasties. A nation-wide multicentre investigation of 8000 cases
Not best available
evidence
Lai, et al.
2007
Presence of medical comorbidities in patients with infected primary hip or knee
arthroplasties
Not best available
evidence
Lawton, et al.
1999
The use of heparin in patients in whom a pulmonary embolism is suspected after total hip
arthroplasty
Not best available
evidence
Lazzarini, et al.
2001
Postoperative infections following total knee replacement: an epidemiological study
Not best available
evidence
Leong, et al.
2006
Duration of operation as a risk factor for surgical site infection: comparison of English and
US data
Not relevant - not
specific to pji
Lonner, et al.
1999
Prodromes of failure in total knee arthroplasty
Does not address
recommendation
Lubbeke, et al.
2008
Outcomes of obese and nonobese patients undergoing revision total hip arthroplasty
Not best available
evidence
27
v0.1 03.25.10
Author
Title
Mac, et al.
1993
Comparison of autoreinfusion and standard drainage systems in total joint arthroplasty
patients
Does not address
recommendation
Malinzak, et al.
2009
Morbidly Obese, Diabetic, Younger, and Unilateral Joint Arthroplasty Patients Have
Elevated Total Joint Arthroplasty Infection Rates
Not best available
evidence
Mandalia, et al.
2008
Evaluation of patients with a painful total knee replacement
Narrative review,
Marchant, et al.
2009
The impact of glycemic control and diabetes mellitus on perioperative outcomes after total
joint arthroplasty
Not relevant - not
specific to pji
McDonald, et al.
1989
Two-stage reconstruction of a total hip arthroplasty because of infection
No comparison group
McLaughlin, et al.
2006
The outcome of total hip replacement in obese and non-obese patients at 10- to 18-years
Not best available
evidence
Meding, et al.
2003
Total Knee Replacement in Patients with Diabetes Mellitus
Not best available
evidence
Menon, et al.
1983
Charnley low-friction arthroplasty in patients with psoriasis
Not best available
evidence
Minnema, et al.
2004
Risk factors for surgical-site infection following primary total knee arthroplasty
Not relevant - not
specific to pji
Mont, et al.
1996
Cementless total knee arthroplasty in obese patients: A comparison with a matched control
group
Not relevant - not
specific to pji
Moran, et al.
2005
Does body mass index affect the early outcome of primary total hip arthroplasty?
Insufficient Data
Muilwijk, et al.
2006
Random effect modelling of patient-related risk factors in orthopaedic procedures: results
from the Dutch nosocomial infection surveillance network 'PREZIES'
Not best available
evidence
28
v0.1 03.25.10
Author
Title
Mulhall, et al.
2006
Current etiologies and modes of failure in total knee arthroplasty revision
Not best available
evidence
Mulier, et al.
1973
Postoperative infection in total hip replacement
Not best available
evidence
Murphy, et al.
1993
The effectiveness of suction drainage in total hip arthroplasty
<25 patients/arm
Murray,
1973
Results in patients with total hip replacement arthroplasty
Insufficient Data
Namba, et al.
2005
Obesity and perioperative morbidity in total hip and total knee arthroplasty patients
Not best available
evidence
Nelson, et al.
2005
Stiffness after total knee arthroplasty. Surgical technique
Does not address
recommendation
Niki, et al.
2006
Phenotypic characteristics of joint fluid cells from patients with continuous joint effusion
after total knee arthroplasty
Not best available
evidence
Niki, et al.
2007
Five types of inflammatory arthritis following total knee arthroplasty
Not best available
evidence
Ong, et al.
2009
Prosthetic Joint Infection Risk After Total Hip Arthroplasty in the Medicare Population
Not best available
evidence
Papagelopoulos, et al.
1996
Long term outcome and survivorship analysis of primary total knee arthroplasty in patients
with diabetes mellitus
Not best available
evidence
Parker, et al.
2004
Closed suction drainage for hip and knee arthroplasty: a meta-analysis
Systematic review,
Parker, et al.
2007
Closed suction surgical wound drainage after orthopaedic surgery
Systematic review,
29
v0.1 03.25.10
Author
Title
Parratte, et al.
2008
The Stiff Total Knee Arthroplasty: A Contemporary Approach
Narrative review,
Partanen, et al.
2006
Impact of deep infection after hip fracture surgery on function and mortality
Not relevant - not
specific to pji
Partio, et al.
1994
Survival of the Townley knee. 360 cases with 8 (0.1-15) years' follow-up
Not best available
evidence
Parvizi, et al.
2007
Does 'excessive' anticoagulation predispose to periprosthetic infection?
Not best available
evidence
Parvizi, et al.
2006
Management of stiffness following total knee arthroplasty
Does not address
recommendation
Pasticci, et al.
2007
Prosthetic infections following total knee arthroplasty: A six-year prospective study (19972002)
Does not address
recommendation
Patel, et al.
2007
Factors associated with prolonged wound drainage after primary total hip and knee
arthroplasty
Not relevant - not
specific to pji
Peersman, et al.
2006
Prolonged operative time correlates with increased infection rate after total knee
arthroplasty
Not best available
evidence
Peersman, et al.
2008
ASA physical status classification is not a good predictor of infection for total knee
replacement and is influenced by the presence of comorbidities
Duplicate data
Perka, et al.
2000
The influence of obesity on perioperative morbidity and mortality in revision total hip
arthroplasty
Not best available
evidence
Petty, et al.
1975
Infection after total knee arthroplasty
Not best available
evidence
Pons, et al.
1999
Infected total hip arthroplasty--the value of intraoperative histology
Composite measure
30
v0.1 03.25.10
Author
Title
Poss, et al.
1984
Factors influencing the incidence and outcome of infection following total joint
arthroplasty
Not best available
evidence
Pritchett, et al.
1991
Knee replacement in morbidly obese women
Not best available
evidence
Ragni, et al.
1995
Postoperative infection following orthopaedic surgery in human immunodeficiency virusinfected hemophiliacs with CD4 counts (less-than or equal to) 200/mm(3)
Not best available
evidence
Ridgeway, et al.
2005
Infection of the surgical site after arthroplasty of the hip
Not relevant - not
specific to pji
Robbins, et al.
2002
Evaluation of pain in patients with apparently solidly fixed total hip arthroplasty
components
Narrative review,
Rodriguez-Merchan,
2007
Total knee replacement in haemophilic arthropathy
Not best available
evidence
Sachs, et al.
2003
Does anticoagulation do more harm than good?: A comparison of patients treated without
prophylaxis and patients treated with low-dose warfarin after total knee arthroplasty
Not best available
evidence
Sadr, et al.
2006
The impact of tobacco use and body mass index on the length of stay in hospital and the
risk of post-operative complications among patients undergoing total hip replacement
Not relevant - not
specific to pji
Schmalzried, et al.
1992
Etiology of deep sepsis in total hip arthroplasty. The significance of hematogenous and
recurrent infections
Not best available
evidence
Scuderi,
2005
The stiff total knee arthroplasty: Causality and solution
Narrative review,
Serna, et al.
1994
Total knee arthroplasty in diabetic patients. Comparison to a matched control group
Not best available
evidence
Shih, et al.
2004
Total knee arthroplasty in patients with liver cirrhosis
Not best available
evidence
31
v0.1 03.25.10
Author
Title
Shrader, et al.
2003
Primary TKA in Patients with Lymphedema
Not best available
evidence
Silva, et al.
2005
Long-term results of primary total knee replacement in patients with hemophilia
Not best available
evidence
Solomon, et al.
2006
Development of a preliminary index that predicts adverse events after total knee
replacement
Does not address
recommendation
Spicer, et al.
2001
Body mass index as a predictor of outcome in total knee replacement
Not best available
evidence
Stern, et al.
1989
Total knee arthroplasty in patients with psoriasis
<25 patients
Stern, et al.
1990
Total knee arthroplasty in obese patients
Does not address
recommendation
Surin, et al.
1983
Infection after total hip replacement. With special reference to a discharge from the wound
Not best available
evidence
Tannenbaum, et al.
1997
Infection around joint replacements in patients who have a renal or liver transplantation
<25 patients
van Loon, et al.
2000
The kinematic total knee arthroplasty. A 10- to 15-year follow-up and survival analysis
Not best available
evidence
Vannini, et al.
1984
Diabetes as pro-infective risk factor in total hip replacement
Not best available
evidence
Varley, et al.
1995
Wound drains in proximal femoral fracture surgery: a randomized prospective trial of 177
patients
Not relevant - not
specific to pji
Waldman, et al.
1997
Total knee arthroplasty infections associated with dental procedures
Does not address
recommendation
32
v0.1 03.25.10
Author
Title
Wang,
1984
Clinical observations on Blauth's total endoprosthesis of the knee joint
Insufficient Data
Weiss, et al.
1993
Persistent wound drainage after primary total knee arthroplasty
<25 patients
Went, et al.
1995
Recurrence of infection after revision of infected hip arthroplasties
No comparison group
White, et al.
1990
Early morbidity after total hip replacement: rheumatoid arthritis versus osteoarthritis
Not relevant - not
specific to pji
Wilson, et al.
1990
Infection as a complication of total knee-replacement arthroplasty. Risk factors and
treatment in sixty-seven cases
Not best available
evidence
Winiarsky, et al.
1998
Total knee arthroplasty in morbidly obese patients
Not best available
evidence
Yasunaga, et al.
2009
Analysis of factors affecting operating time, postoperative complications, and length of
stay for total knee arthroplasty: Nationwide web-based survey
Not relevant - not
specific to pji
Yasunaga, et al.
2009
High-volume surgeons in regard to reductions in operating time, blood loss, and
postoperative complications for total hip arthroplasty
Not relevant - not
specific to pji
Yong, et al.
2001
Risk factors for infection in total hip replacement surgery at Hospital Kuala Lumpur
Not relevant - not
specific to pji
Zamora-Navas, et al.
1999
Closed suction drainage after knee arthroplasty. A prospective study of the effectiveness of
the operation and of bacterial contamination
<25 patients per group
33
v0.1 03.25.10
Spectrum bias avoided
Selection criteria described
Appropriate reference standard
Disease progression bias avoided
Partial verification bias avoided
Differential verification bias
avoided
Incorporation bias avoided
Index test execution described
Reference standard execution
described
Test review bias avoided
Diagnostic review bias avoided
Clinical review bias avoided
Uninterpretable/Intermediate test
result(s) reported
Withdrawals explained
STUDY QUALITY
Table 9. Quality of Diagnostic Studies
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
IV
○
●
●
●
●
●
●
●
●
●
?
●
●
●
IV
○
●
●
●
●
●
●
●
?
●
?
●
●
●
IV
○
●
●
●
●
●
●
●
?
●
?
●
●
●
IV
IV
V
○
○
?
●
●
○
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
?
?
●
●
●
?
?
?
●
●
●
●
●
●
●
●
●
●
● = Yes
○ = No
? = Unclear
Author
N
Lachiewicz
142
Teller
161
Magnuson
98
Magnuson
98
Magnuson
Magnuson
Virolainen
98
98
68
Index Test
Implant in situ <5
years
Local signs
(erythema,
warmth, edema)
Warmth
Swelling or
erythema
Sinus tract
Pain
Pain
Level of
Evidence
34
v0.1 03.25.10
prospective
Joint
Level of Evidence
sufficient events per variable (10)
collinearity tested or not relevant
goodness of fit stats reported
model validation
N
sufficient patients per variable (10)
fitting procedure stated
Risk Factor
all variables discussed in results
unambiguous coding
Author
variables identified in Methods
Table 10. Quality of Prognostic Studies
Wymenga
Hematoma
2547
Hip
II
●
○
?
●
○
●
○
●
○
○
Wymenga
Hematoma
345
Knee
II
●
○
?
●
○
●
○
●
○
○
Pulido
Hematoma/ wound drainage
9245
Mixed
III
○
●
●
●
○
●
○
●
○
○
Smabrekke
Operating time
28020
Hip
II
●
●
○
●
●
●
●
●
○
○
Huotari
Operating time
5614
Hip
II
●
●
●
●
○
●
○
●
○
○
Huotari
Operating time
4217
Knee
II
●
●
●
●
○
●
○
●
○
○
Wymenga
Operating time
2547
Hip
II
●
○
?
●
○
●
○
●
○
○
Wymenga
Operating time
345
Knee
II
●
○
?
●
○
●
○
●
○
○
Jamsen
Prior infection
819
Knee
II
Berbari
Prior joint infection
924
Mixed
IV (case-control)
○
○
●
●
●
●
●
●
○
●
Huotari
Rheumatoid arthritis
5614
Hip
II
●
●
●
●
○
●
○
●
○
○
● = Yes
○ = No
? = Not Reported
n/a = Not Applicable
Multiple Regression of Joint Registry Data
(see below for registry quality)
35
v0.1 03.25.10
prospective
Joint
Level of Evidence
model validation
N
Risk Factor
unambiguous coding
Author
Table 10. Quality of Prognostic Studies (Continued)
Huotari
4217
Knee
II
●
●
●
●
○
●
○
●
○
○
Wymenga
Diabetes
2547
Hip
II
●
○
?
●
○
●
○
●
○
○
Wymenga
Use of steroids
2547
Hip
II
●
○
?
●
○
●
○
●
○
○
Wymenga
Diabetes
345
Knee
II
●
○
?
●
○
●
○
●
○
○
Wymenga
Use of steroids
345
Knee
II
●
○
?
●
○
●
○
●
○
○
Jamsen
primary: 38338
revision: 2061
Knee
II
Lubbeke
Obesity
(BMI ≥30)
2495
Hip
II
●
●
●
●
○
●
●
●
○
○
Dowsey
Obesity
1207
Hip
III
○
●
●
●
●
●
●
●
○
○
Amin
Obesity
82
Knee
II
●
●
●
n/a
○
●
●
●
○
○
Bordini
Obesity
9735
Knee
II
● = Yes
○ = No
? = Not Reported
36
v0.1 03.25.10
prospective
Joint
Level of Evidence
model validation
N
Risk Factor
unambiguous coding
Author
Table 10. Quality of Prognostic Studies (Continued)
Pulido
Obesity
(BMI >40)
9245
Mixed
III
○
●
●
●
○
●
○
●
○
○
Dowsey
Smoking
1214
Knee
III
○
●
●
●
○
●
○
○
○
○
Peersman
Smoking
349
Knee
IV (case-contol)
○
○
○
?
?
●
●
●
●
○
Khan
Smoking
1767
Hip
V (univariate)
●
n/a
n/a
n/a
n/a
n/a
n/a
n/a
n/a
n/a
Wymenga
Wound infection
2547
Hip
II
●
○
?
●
○
●
○
●
○
○
Wymenga
Wound infection
345
Knee
II
●
○
?
●
○
●
○
●
○
○
Pulido
Wound infection
9245
Mixed
III
○
●
●
●
○
●
○
●
○
○
Saleh
Surgical site infection
97
Mixed
III
○
●
●
n/a
○
●
●
●
○
○
● = Yes
○ = No
? = Not Reported
37
v0.1 03.25.10
Mandatory Data
Submission
Validated Data
Author
Risk Factor
N
Joint
Level of
Evidence
Population-Based Registry
>90% of patients captured
Statistical Quality Control
Measures Performed
Ensures correct diagnosis
Table 11. Risk Factors - Quality of Joint Registries
Jamsen
Prior infection
(reason for revision
was infection)
819
Knee
II
●
●
○
●
?
●
Jamsen
primary: 38338
revision: 2061
Knee
II
●
●
○
●
?
●
Bordini
Obesity
9735
Knee
II
●
●
?
●
?
●
● = Yes ○ = No ? = Not Reported
38
v0.1 03.25.10
Assessor Blind
Control
N
Level of
Evidence
>80% Follow-Up
Treatment
Allocation Concealment
Subjects Blind
Author
Stochastic Randomization
Similar in Outcome at
Baseline
Table 12. Risk Factors - Quality of Randomized Trials
Confalonieri
Crevoisier
Esler
Gonzalez Della
Valle
Holt
Jenny
Johansson
Kim
Kim
Niskanen
Ovadia
Ritter
Walmsley
Drain
Drain
Drain
No Drain
No Drain
No Drain
78
98
100
II
II
II
?
?
?
●
●
●
○
○
○
○
○
○
●
●
●
●
●
●
● = Yes ○ = No ? = Not Reported
Bergqvist
Drain
Drain
Drain
Drain
Drain
Drain
Drain
Drain
Drain
Drain
No Drain
No Drain
No Drain
No Drain
No Drain
No Drain
No Drain
No Drain
No Drain
No Drain
No
Thromboprophylaxis
Thromboprophylaxis
II
104
137
60
105
138
96
97
88
415
577
II
II
II
II
II
II
II
II
II
●
○
?
?
●
●
?
?
?
?
○
○
●
●
●
●
○
●
○
●
○
○
○
○
○
○
○
○
○
○
○
○
○
○
○
○
○
○
○
○
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
161
II
?
○
○
○
●
●
39
v0.1 03.25.10
STUDY RESULTS
Table 13. Pain as a Predictor of Periprosthetic Infection
Level of
Evidence
Author
N
Test
IV
Magnuson
98
Pain
V
Virolainen 68
Pain
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
Mixed
1
-
1
(0.93, 1)
0
(0, .07)
50
48
0
0
Mixed
1.18
(1.06, 1.31)
0
1
(0.66, 1)
.15
(.07, .27)
9
50
0
9
Sensitivity
(95% CI)
Specificity
(95% CI)
0.12
(0.05,
0.24)
0.24
(0.13,
0.38)
0.96
(0.86,
0.99)
0.90
(0.77,
0.97)
0.18
(0.05,
0.40)
1
(0.97, 1)
Reference
Standard
Intraoperative
Cultures or
Histology
Intraoperative
Cultures
TP FP FN TN
Table 14. Warmth, Erythema, Swelling as Predictors of Periprosthetic Infection
Level of
Evidence
Author
N
Test
IV
Magnuson
98
Warmth
IV
Magnuson
98
IV
Teller
161
Swelling
or
Erythema
Local
Signs
(erythema,
warmth,
edema)
Reference
Standard
Intraoperative
Cultures or
Histology
Intraoperative
Cultures or
Histology
Intraoperative
Cultures or
Frank
Purulence
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Mixed
2.88
(0.61, 13.6)
0.92
(0.82, 1.03)
Mixed
2.3
(0.88, 6.05)
0.85
(0.71, 1.02)
Mixed
-
0.82
(0.67, 0.99)
TP FP FN
TN
6
2
44
46
12
5
38
43
4
0
18
139
40
v0.1 03.25.10
Table 15. Early Implant Failure as a Predictor of Periprosthetic Infection
Level of
Evidence
I
Author
N
Lachiewicz 142
Test
Reference
Standard
Implant
in situ
<5 years
Intraoperative
Cultures or
Gross
Purulence
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
TP FP FN TN
Hip
2.1
(1.36, 3.25)
0.53
(0.29, 0.96)
0.63
(0.38, 0.84)
0.70
(0.61, 0.78)
12
37
7
86
Table 16. Sinus Tract as a Predictor of Periprosthetic Infection
Level of
Evidence
Author
Risk Factor
Joint
N
Results
IV
Magnuson
sinus tract
Mixed
98
OR undefined - all 7 with sinus
tract had infection (p=.01)
Table 17. Prevalence of Periprosthetic Infection among Patients with Bacteremia
Level of
Evidence
Author
Risk Factor
N
Infections
%
V
Murdoch
S. aureus bacteremia
53
24 hematogenous,
9 primary
45% hematogenous,
62% overall
41
v0.1 03.25.10
Table 18. Prevalence of Periprosthetic Infection among Patients with Metachronous Periprosthetic Infection
Level of
Evidence
V
V
Author
Risk Factor
N
Infections
%
Luessenhop
Murray
Metachronous PJI
Metachronous PJI
145
68
27
10
19%
15%
Table 19. Anticoagulation RCT
Level of
Evidence
Author
Risk Factor
Joint
N
Results
II
Bergqvist
Anticoagulation
Hip
161
(RCT with no infections)
42
v0.1 03.25.10
Table 20. Use of Drains RCTs
Level of
Evidence
II
II
II
Author
Risk Factor
Joint
N
Esler
Kim
Walmsley
Drains
Drains
Drains
Knee
Knee
Hip
100
138
577
II
Confalonieri
Drains
Knee
78
II
Crevoisier
Drains
Mixed
98
II
Gonzalez
Della Valle
Drains
Hip
104
II
Holt
Drains
Knee
137
II
Jenny
Drains
Knee
60
II
Johansson
Drains
Hip
105
II
Kim
Drains
Hip
96
II
Niskanen
Drains
Mixed
97
II
Ovadia
Drains
Mixed
88
II
Ritter
Drains
Mixed
415
Results
Odds Ratio (95% CI)
0 (0, 39)
0 (0, 5.3)
1.05 (.08, 14.5)
(no infections)
(no infections)
(no infections)
(no infections)
(no infections)
(no infections)
(no infections)
(no infections)
(no infections)
(no infections)
43
v0.1 03.25.10
RECOMMENDATION 2
We recommend erythrocyte sedimentation rate and C-reactive protein testing for patients
assessed for periprosthetic joint infection.
Rationale
Six Level I studies evaluating the ESR,11, 21, 37, 48, 93, 96 six Level I studies evaluating the
CRP,11, 21, 31, 37, 93, 96 and two Level I studies evaluating the combined use of ESR and
CRP 37, 96 were used for analysis.
The use of screening inflammatory markers (ESR and CRP) is the starting point in the
work-up investigations for the diagnosis or exclusion of periprosthetic joint infection.
Our systematic review of the literature found strong evidence for using both ESR and
CRP testing. We recommend use of this combination of tests to “rule out” infection.
The combined use of ESR and CRP is a very good “rule out” test. When both the ESR
and CRP are negative, periprosthetic infection is unlikely (negative likelihood ratio 0 –
0.06). When both tests are positive, periprosthetic infection must be considered (positive
likelihood ratio 4.3 – 12.1), and this result warrants further investigations. However, the
clinician also needs to be aware of other inflammatory conditions such as rheumatoid
arthritis, neoplasms, coronary artery disease, polymyalgia rheumatica, inflammatory
bowel disease, etc. that can lead to elevation of inflammatory markers. The use of either
test alone is less reliable for either ‘ruling out’ or ‘ruling in’ infection than when both
tests are combined. A negative ESR is better at ‘ruling out’ infection than a positive
result is for ‘ruling in’ infection (better negative likelihood ratio than positive likelihood
ratio). Similarly, the CRP is a better test for ‘ruling out’ infection, but somewhat better
than the ESR at ‘ruling in’ infection.
The evidence strongly supports obtaining an ESR and CRP in all patients being assessed
for periprosthetic infection.
Supporting Evidence
The systematic review for this recommendation included studies investigating the
diagnostic utility of not only ESR and CRP, but also radiographs and peripheral white
blood cell counts. With the exception of two studies that investigated the joint use of ESR
and CRP, 37, 96 there are no data looking at the use of a combination of these tests. The
available data are from studies that investigated each test in isolation.
For erythrocyte sedimentation rates, we included three studies of hip patients, two of
knee patients, and one of mixed hip and knee patients. 11, 21, 37, 48, 93, 96 All studies
produced reliable data. Meta-analysis of all ESR studies indicated that threshold effects
may be responsible for much of the differences between studies. Using a threshold of 30
mm/hr, a positive result produced a small (but sometimes important) change in the
44
v0.1 03.25.10
probability of infection, while a negative result produced a moderate change (see Figure
5).
For C-reactive protein, we included two studies of hip patients, three of knee patients,
and one of mixed hip and knee patients. 11, 21, 31, 37, 93, 96 All studies produced reliable data.
Meta-analysis of all CRP studies indicated significant between-study heterogeneity (I2
=83%), and adjusting for differences in thresholds did not explain the variation between
studies. With the exception of one study with wide confidence intervals,93 the positive
and negative likelihood ratios were statistically significant (see Table 25).
We included two studies with reliable data that looked at using a combination of ESR and
CRP to diagnose infection.37, 96 A negative result on both tests was very good at ruling
out infection. A positive result on one of the tests produced a small (likelihood ratio <5)
change in probability, so it was not very good at ruling in infection. A positive result on
both tests was a better “rule in” test (see Table 26).
For radiographs, we included one study of hip patients with reliable data,19 one study of
hip patients with moderately reliable data,9 and one study of knee patients with
moderately reliable data.5 There was no consistent evidence of statistically significant
diagnostic benefit (see Table 27) however, findings such as periostitis or early osteolysis
may indicate infection. In addition, radiographs can provide alternative explanations for
joint pain or dysfunction and are routinely obtained in the evaluation of the painful or
failed hip or knee arthroplasty.
For peripheral white blood cell counts, we included three studies of hip patients and one
of mixed hip and knee patients with reliable data.11, 83, 93, 99 We included three additional
studies of mixed hip and knee patients with moderately reliable data.8, 23, 105 The
thresholds differed in each study. Meta-analysis of all peripheral white blood cell count
studies indicated significant between-study heterogeneity (I2 =98%), and adjusting for
differences in thresholds did not explain the variation between studies. With the
exception of one study with wide confidence intervals,93 the positive and negative
likelihood ratios were statistically significant (see Table 28).
45
v0.1 03.25.10
SUMMARY OF EVIDENCE
Table 21. Radiography and Serology Summary of Evidence
Test
Number
of
Studies
Positive
Likelihood Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
ESR – metaanalysis
(I2=26%)
6
2.9
(1.7, 4.8)
0.15
(0.09, 0.27)
0.90
(0.82, 0.94)
0.69
(0.51, .82)
CRP (range)
6
2.4 – 27.1
0.05 – 0.8
0.30 – 0.95
0.71 – 0.96
ESR and CRP 2
4.34 – 12.1
0.14 - 0.21
0.80 – 0.89
0.79 – 0.93
positive if both
positive (range)
ESR and CRP positive if one
2
1.74 – 4.22
0 – 0.06
0.96 - 1
0.43 – 0.77
positive (range)
Radiograph –
2
1.2 – 2.99
0.55 – 0.95
0.25 – 0.55
0.79 – 0.82
lucency (range)
Radiograph –
periostitis
2
1.04 – 20.8
0.82 - 0.92
0.17 – 0.70
0.33 - 1
(range)
Radiograph –
other measures
3
0.52 – 2.4
0.3 - 1.23
0.17 – 0.80
0.67 – 0.84
(range)
WBC (range)
7
1.77 – 8.45
0.08 – 0.89
0.10 – 0.94
0.60 -1
*Range presented when fewer than four studies or when meta-analysis indicated heterogeneity
46
v0.1 03.25.10
EXCLUDED ARTICLES
Author
Austin, et al.
2008
Title
A simple, cost-effective screening protocol to rule out periprosthetic infection
Not best available
evidence
Bare, et al.
2006
Preoperative evaluations in revision total knee arthroplasty
Not best available
evidence
Bergstrom, et al.
1974
Radiographic abnormalities caused by postoperative infection following total hip
arthroplasty
<25 patients/arm
Canner, et al.
1984
The infected hip after total hip arthroplasty
Not relevant - not
diagnostic study
Carlsson, et al.
1978
Erythrocyte sedimentation rate in infected and non-infected total-hip arthroplasties
<25 patients/arm
Chevillotte, et al.
2008
Inflammatory Laboratory Markers in Periprosthetic Hip Fractures
Not best available
evidence
Choudhry, et al.
1992
Plasma viscosity and C-reactive protein after total hip and knee arthroplasty
Not relevant - not
diagnostic study
Chryssikos, et al.
2008
FDG-PET imaging can diagnose periprosthetic infection of the hip
Not best available
evidence
Covey, et al.
1987
Clinical significance of the erythrocyte sedimentation rate in orthopaedic surgery
Narrative review,
Duff, et al.
1996
Aspiration of the knee joint before revision arthroplasty
Not best available
evidence
Dupont, et al.
2008
The value of C-reactive protein for postoperative monitoring of lower limb arthroplasty
Not relevant - not
specific to pji
Eisler, et al.
2001
Ultrasound for diagnosis of infection in revision total hip arthroplasty
Insufficient Data
47
v0.1 03.25.10
Author
Title
Feldman, et al.
1995
The role of intraoperative frozen sections in revision total joint arthroplasty
Not best available
evidence
Forster, et al.
1982
Sedimentation rate in infected and uninfected total hip arthroplasty
Not best available
evidence
Ghanem, et al.
2008
Determining 'true' leukocytosis in bloody joint aspiration
Not best available
evidence
Ghanem, et al.
2009
The use of receiver operating characteristics analysis in determining erythrocyte
sedimentation rate and C-reactive protein levels in diagnosing periprosthetic infection prior
to revision total hip arthroplasty
Not best available
evidence
Ginai, et al.
1996
Digital subtraction arthrography in preoperative evaluation of painful total hip arthroplasty
Not relevant - not
specific to pji
Itasaka, et al.
2001
Diagnosis of infection after total hip arthroplasty
Not best available
evidence
Lachiewicz, et al.
1996
Aspiration of the hip joint before revision total hip arthroplasty. Clinical and laboratory
factors influencing attainment of a positive culture
Not best available
evidence
Levitsky, et al.
1991
Evaluation of the painful prosthetic joint. Relative value of bone scan, sedimentation rate,
and joint aspiration
Not best available
evidence
Lyons, et al.
1985
Evaluation of radiographic findings in painful hip arthroplasties
Not best available
evidence
Magnuson, et al.
1988
In-111-labeled leukocyte scintigraphy in suspected orthopedic prosthesis infection:
comparison with other imaging modalities
Not best available
evidence
Maury, et al.
1984
Control of the acute-phase serum amyloid A and C-reactive protein response: comparison
of total replacement of the hip and knee
Not relevant - not
diagnostic study
Miniaci, et al.
1990
Analysis of radionuclide arthrograms, radiographic arthrograms, and sequential plain
radiographs in the assessment of painful hip arthroplasty
Not relevant - not
specific to pji
48
v0.1 03.25.10
Author
Title
Moreschini, et al.
2001
Postoperative physiopathological analysis of inflammatory parameters in patients
undergoing hip or knee arthroplasty
Not relevant - not
diagnostic study
Mulier, et al.
1973
Postoperative infection in total hip replacement
Not best available
evidence
Muller, et al.
2008
Diagnosis of periprosthetic infection following total hip arthroplasty - evaluation of the
diagnostic values of pre- and intraoperative parameters and the associated strategy to
preoperatively select patients with a high probability of joint infection
Not best available
evidence
NilsdotterAugustinsson, et al.
2007
Inflammatory response in 85 patients with loosened hip prostheses: a prospective study
comparing inflammatory markers in patients with aseptic and septic prosthetic loosening
Not best available
evidence
Niskanen, et al.
1996
Serum C-reactive protein levels after total hip and knee arthroplasty
Not relevant - not
diagnostic study
Okafor, et al.
1998
Postoperative changes of erythrocyte sedimentation rate, plasma viscosity and C-reactive
protein levels after hip surgery
Not relevant - not
diagnostic study
Panousis, et al.
2005
Poor predictive value of broad-range PCR for the detection of arthroplasty infection in 92
cases
Not best available
evidence
Park, et al.
2008
Normative Temporal Values of CRP and ESR in Unilateral and Staged Bilateral TKA
Not relevant - not
diagnostic study
Parvizi, et al.
2008
Diagnosis of infected total knee: findings of a multicenter database
Insufficient Data
Rosas, et al.
1998
Contribution of laboratory tests, scintigraphy, and histology to the diagnosis of lower limb
joint replacement infection
Insufficient Data
Sanzen, et al.
1988
The erythrocyte sedimentation rate following exchange of infected total hips
<25 patients/arm
Sanzen, et al.
1989
The diagnostic value of C-reactive protein in infected total hip arthroplasties
Not best available
evidence
49
v0.1 03.25.10
Author
Title
Sanzen, et al.
1997
Periprosthetic low-grade hip infections. Erythrocyte sedimentation rate and C-reactive
protein in 23 cases
<25 patients
Schneider, et al.
1982
Radiologic evaluation of painful joint prostheses
Narrative review,
Schulak, et al.
1982
The erythrocyte sedimentation rate in orthopaedic patients
Narrative review,
Schwenger, et al.
1998
CRP levels in autoimmune disease can be specified by measurement of procalcitonin
Not relevant - not
specific to pji
Sciuk, et al.
1992
White blood cell scintigraphy with monoclonal antibodies in the study of the infected
endoprosthesis
Not best available
evidence
Shih, et al.
1987
Erythrocyte sedimentation rate and C-reactive protein values in patients with total hip
arthroplasty
Not best available
evidence
Simon, et al.
2004
Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a
systematic review and meta-analysis
Not relevant - not
specific to pji
Stumpe, et al.
2004
FDG PET for differentiation of infection and aseptic loosening in total hip replacements:
comparison with conventional radiography and three-phase bone scintigraphy
Not best available
evidence
Sudanese, et al.
1994
Diagnostic protocol in prosthetic loosening
Not best available
evidence
Tehranzadeh, et al.
1981
Radiological evaluation of painful total hip replacement
Not best available
evidence
Teller, et al.
2000
Sequential indium-labeled leukocyte and bone scans to diagnose prosthetic joint infection
Not best available
evidence
Thoren, et al.
1991
Erythrocyte sedimentation rate in infection of total hip replacements
Not best available
evidence
Uzzan, et al.
2006
Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or
trauma: a systematic review and meta-analysis
Not relevant
50
v0.1 03.25.10
Author
Title
Virolainen, et al.
2002
Walker, et al.
1991
White, et al.
1998
Not best available
evidence
Not relevant - not
specific to pji
Not relevant - not
diagnostic study
The reliability of diagnosis of infection during revision arthroplasties
Arthrography of painful hips following arthroplasty: digital versus plain film subtraction
C-reactive protein level after total hip and total knee replacement
N
Index Test
avoided
described
result(s) reported
Author
Level of
Evidence
STUDY QUALITY
Table 23. Radiography and Serology - Quality
Savarino
26
ESR (>15mm/hr)
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
Savarino
26
ESR (>15mm/hr)
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
Savarino
26
ESR (>15mm/hr)
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
Schinsky
201
ESR (>30 mm/hr)
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
● = Yes
○ = No
? = Unclear
51
v0.1 03.25.10
described
result(s) reported
ESR (>50 mm/hr)
ESR (>50 mm/hr)
ESR (>50 mm/hr)
ESR (>30mm/hr)
ESR (>22.5 mm/hr)
ESR (>30 mm/hr)
ESR (>32 mm/hr)
ESR (>30 mm/hr)
CRP (>0.5mg/dL)
CRP (>0.5mg/dL)
CRP (>0.5mg/dL)
CRP (>1 mg/dL)
CRP (>2 mg/dL)
CRP (>2 mg/dL)
CRP (>2 mg/dL)
CRP (>1.0 mg/dL)
26
26
26
63
151
151
78
94
26
26
26
201
26
26
26
151
avoided
Savarino
Savarino
Savarino
Kamme
Greidanus
Greidanus
Bottner
Della Valle
Savarino
Savarino
Savarino
Schinsky
Savarino
Savarino
Savarino
Greidanus
Level of
Evidence
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
Index Test
N
Author
● = Yes
○ = No
? = Unclear
Table 23. Radiography and Serology – Quality (Continued)
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
?
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
?
?
●
●
●
●
●
●
●
●
●
?
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
?
?
●
●
●
?
?
●
?
?
?
●
?
?
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
52
v0.1 03.25.10
avoided
described
result(s) reported
Level of
Evidence
I
I
I
I
I
I
I
I
I
I
●
●
●
●
●
●
●
●
●
●
●
●
?
?
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
?
●
●
●
●
?
?
?
?
●
●
●
●
●
●
●
●
●
●
●
●
?
?
?
?
●
●
●
●
?
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
I
●
●
●
●
●
●
●
●
●
●
●
?
●
●
I
●
●
●
●
●
●
●
●
●
●
●
?
●
●
I
●
●
●
●
●
●
●
●
●
●
●
?
●
●
● = Yes
○ = No
? = Unclear
Author
N
Index Test
Greidanus
Fink
Bottner
Bottner
Della Valle
Greidanus
Greidanus
Greidanus
Greidanus
Schinsky
151
145
78
78
94
151
151
151
151
201
Cyteval
65
Cyteval
65
Cyteval
65
CRP (>1.35 mg/dL)
CRP (>1.35 mg/dL)
CRP (>1.5 mg/dL)
CRP (>3.2 mg/dL)
CRP (>1 mg/dL)
ESR and CRP (22.5/1.35)
ESR and CRP (30/1.0)
ESR or CRP (22.5/1.35)
ESR or CRP (30/1.0)
ESR or CRP (30/1.0)
radiograph - asymmetric
position of femoral head
radiograph - bone
abnormalities (focal or
nonfocal lucency,
periostitis)
radiograph - focal lucency
53
v0.1 03.25.10
avoided
described
result(s) reported
I
●
●
●
●
●
●
●
●
●
●
●
?
●
●
I
II
●
●
●
●
●
?
●
●
●
●
●
●
●
●
●
○
●
●
●
●
●
?
?
●
●
●
●
●
III
●
●
●
●
●
●
●
●
●
●
○
●
●
●
III
●
●
●
●
●
●
●
●
●
●
○
●
●
●
III
●
●
●
●
●
●
●
●
●
●
○
●
●
●
III
I
I
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
○
?
●
?
●
●
●
●
●
●
●
●
●
●
●
●
● = Yes
○ = No
? = Unclear
Author
N
Cyteval
65
Cyteval
Bernay
65
31
Barrack
69
Barrack
69
Barrack
69
Barrack
Spangehl
Savarino
Savarino
69
202
26
26
Index Test
radiograph - nonfocal
lucency
radiograph - periostitis
radiograph
radiograph: complete
radiolucent line adjacent to
tibial component
radiograph: gross loosening
radiograph: Knee Society
Grade 3 classification for
tibial component
radiolucency in addition to
Grade 1 under femoral
component
radiograph: periostitis
WBC (>11.0*10^9/L)
WBC (>9500/mm^3)
WBC (>9500/mm^3)
Level of
Evidence
54
v0.1 03.25.10
avoided
described
result(s) reported
Level of
Evidence
I
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
?
?
●
●
●
●
●
●
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
I
II
●
●
?
●
●
●
●
●
●
●
●
●
●
●
●
●
●
○
●
●
?
?
●
●
●
●
●
●
II
?
●
●
●
●
●
●
●
○
●
●
●
●
○
II
?
●
●
●
●
●
●
●
●
●
?
●
●
○
● = Yes
○ = No
? = Unclear
Author
N
Index Test
Savarino
Pill
26
92
Spangehl
202
Bottner
Di Cesare
78
58
Bernard
228
Trampuz
296
WBC (>9500/mm^3)
WBC (>11000/μL)
WBC differential (>75%
neutrophils)
WBC (>6200/μL)
WBC (>11.0*10^9)
Polynuclear neutrophil
count (≥6000 cells/ml)
WBC (>10x10^9/L)
55
v0.1 03.25.10
STUDY RESULTS
Figure 5. ESR Meta-analysis Results - Likelihood Ratios
StudyId
StudyId
Savarino - 15mm/hr
Savarino - 15mm/hr
Greidanus - 22.5mm/hr
Greidanus - 22.5mm/hr
Schinsky - 30mm/hr
Schinsky - 30mm/hr
Kamme - 30mm/hr
Kamme - 30mm/hr
Della Valle - 30mm/hr
Della Valle - 30mm/hr
Bottner - 32mm/hr
Bottner - 32mm/hr
COMBINED
COMBINED
1
2
5
10
.1 .2
.5
1
DLR NEGATIVE
DLR POSITIVE
INTERPRETING THE FOREST PLOTS
Throughout the guideline we use descriptive diagrams or forest plots to present data from
studies comparing a diagnostic test to a reference standard. The positive and negative
likelihood ratios are the effect measures used to depict study results. The horizontal line
running through each point represents the 95% confidence interval for that point. In the
graphs above, the solid vertical line represents “no effect” where the likelihood ratio is
equal to one. The dashed line represents the value of a likelihood ratio that indicates a
large and conclusive change in the probability of disease.
For example, in the figures above, the summary estimate (indicated by the diamond)
indicates a positive likelihood ratio close to 3 and a negative likelihood ratio of between
0.2 and 0.1. This result is statistically significant because the 95% Confidence Interval
does not cross the “no effect” line. Also please note that summary measures (diamond)
are not reported in the plot if high heterogeneity (>50%) is present.
56
v0.1 03.25.10
Figure 6. CRP Results - Likelihood Ratios
StudyId
StudyId
Savarino - 0.5mg/dL
Savarino - 0.5mg/dL
Della Valle - 1 mg/dL
Della Valle - 1 mg/dL
Schinsky - 1 mg/dL
Schinsky - 1 mg/dL
Greidanus - 1 mg/dL
Greidanus - 1 mg/dL
Fink - 1.35 mg/dL
Fink - 1.35 mg/dL
Greidanus - 1.35 mg/dL
Greidanus - 1.35 mg/dL
Bottner - 1.5 mg/dL
Bottner - 1.5 mg/dL
Savarino - 2 mg/dL
Savarino - 2 mg/dL
Bottner - 3.2 mg/dL
Bottner - 3.2 mg/dL
1 2 5 10
.1.2
DLR POSITIVE
.5
1
DLR NEGATIVE
Figure 7. ESR and CRP - Likelihood Ratios
StudyId
StudyId
Greidanus – both positive (22.5/1.35)
Greidanus – both positive (22.5/1.35)
Greidanus – both positive (30/1.0)
Greidanus – both positive (30/1.0)
Schinsky - both positive (30/1.0)
Schinsky - both positive (30/1.0)
Greidanus – 1 or both positive (22.5/1.35)
Greidanus – 1 or both positive (22.5/1.35)
Greidanus – 1 or both positive (30/1.0)
Greidanus – 1 or both positive (30/1.0)
Schinsky – 1 or both positive (30/1.0)
Schinsky – 1 or both positive (30/1.0)
1
2
5
10
.1.2
DLR POSITIVE
.5
1
DLR NEGATIVE
57
v0.1 03.25.10
Figure 8. Radiography Results - Likelihood Ratios
StudyId
StudyId
Barrack - periostitis
Barrack - periostitis
Barrack - radiolucency grade
Barrack - radiolucency grade
Barrack - gross loosening
Barrack - gross loosening
Barrack - radiolucent line
Barrack - radiolucent line
Bernay - plain radiograph
Bernay - plain radiograph
Cyteval - periostitis
Cyteval - nonfocal lucency
Cyteval - nonfocal lucency
Cyteval - focal lucency
Cyteval - focal lucency
Cyteval - bone abnormalities
Cyteval - femoral head asymmetry
1 2
5 10
.1 .2
DLR POSITIVE
.5
1
DLR NEGATIVE
Figure 9. White Blood Cell Count Results - Likelihood Ratios
StudyId
StudyId
Bernard
Bernard
Trampuz
Trampuz
Di Cesare
Di Cesare
Bottner
Bottner
Spangehl - % neutrophils
Spangehl - % neutrophils
Pill
Pill
Savarino
Savarino
Spangehl - WBC count
Spangehl - WBC count
1 2
5 10
.1 .2
DLR POSITIVE
0.5
1
DLR NEGATIVE
58
v0.1 03.25.10
Table 24. Erythrocyte Sedimentation Rate Results
Level of
Evidence
Author
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
1.09
(0.43, 2.8)
0.56
(0.3, 0.8)
0.97
(0.39, 2.4)
N
Test
Intraoperative
Cultures
Hip
0.94
(0.48, 1.82)
Histology
Hip
1.02
(0.53, 1.97)
Hip
1.07
0.91
(0.55, 2.08) (0.36, 2.34)
Hip
1.58
0.09
(1.37, 1.82) (0.02, 0.37)
I
Savarino
26
ESR
(15mm/hr)
I
Savarino
26
ESR
(15mm/hr)
I
Savarino
26
ESR
(15mm/hr)
I
Schinsky 201
ESR
(30
mm/hr)
Savarino
ESR
(50
mm/hr)
I
Joint
Positive
Likelihood
Ratio
(95% CI)
Reference
Standard
26
Intraoperative
cultures and
histology
at least 2 of: 1)a
positive
intraoperative
culture (on solid
media) 2)gross
purulence 3)final
histopathological
result consistent
with infection
(average of >10
PMN in the 5
most cellular high
power fields)
Intraoperative
Cultures
Hip
3.75
(0.53,
26.73)
0.69
(0.45, 1.07)
Specificity
TP FN FP
(95% CI)
0.4
(0.12,
0.74)
0.43
(0.18,
0.71)
TN
9
7
6
4
7
5
8
6
0.44
(0.2, 0.7)
6
4
9
7
0.96
(0.87, 1)
0.39
(0.31,
0.47)
53
2
89
57
0.38
(0.15,
0.65)
0.9
(0.55, 1)
6
10
1
9
0.58
(0.28,
0.85)
0.6
(0.26,
0.88)
59
v0.1 03.25.10
Table 24. Erythrocyte Sedimentation Rate Results (Continued)
Level of
Evidence
Author
N
I
Savarino
26
I
Savarino
26
I
Kamme
63
I
Greidanus 151
I
Greidanus 151
Test
Reference
Standard
Joint
Positive
Likelihood
Ratio
(95% CI)
7
(0.97,
50.27)
9.6
(1.35,
68.43)
Negative
Likelihood
Ratio
(95% CI)
ESR
(50
mm/hr)
ESR
(50
mm/hr)
Histology
Hip
Intraoperative
cultures and
histology
Hip
ESR
(30mm/hr)
Intraoperative
Cultures
Hip
3.2
0.15
(1.69, 6.05) (0.06, 0.38)
ESR
(22.5
mm/hr)
ESR
(30
mm/hr)
Cultures –
Intraoperative
or Aspiration
Cultures –
Intraoperative
or Aspiration
Knee
5.5
0.08
(3.58, 8.43) (0.03, 0.24)
Knee
6.7
(3.96,
11.36)
0.54
(0.3, 0.97)
0.43
(0.2, 0.92)
0.2
(0.11, 0.38)
Sensitivity
(95% CI)
0.5
(0.21,
0.79)
0.6
(0.26,
0.88)
0.89
(0.75,
0.97)
0.93
(0.82,
0.99)
0.82
(0.68,
0.92)
Specificity
TP FN FP
(95% CI)
TN
0.93
(0.66, 1)
6
6
1
13
0.94
(0.7, 1)
6
4
1
15
0.72
(0.51,
0.88)
34
4
7*
18
0.83
(0.74, 0.9)
42
3
18
88
0.88
(0.8, 0.93)
37
8
13
93
60
v0.1 03.25.10
Table 24. Erythrocyte Sedimentation Rate Results (Continued)
Level of
Evidence
I
Author
Della
Valle
N
94
Test
Reference
Standard
ESR
(30
mm/hr)
at least 2 of 3
positive
intraoperative
cultures on
solid media or if
2 of following:
1)at least 1
positive culture
2)final
histopathology
consistent with
infection
3)gross
purulence seen
at time of
revision
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Knee
2.66
(1.8, 3.92)
0.15
(0.06, 0.38)
0.9
(0.77,
0.97)
Specificity
TP FN FP
(95% CI)
0.66
(0.52,
0.78)
37
4
18
Mixed
(50
0.81
7.69
0.89
0.21
I
Bottner
78
17
4
6
hip,
(3.51,
(0.58,
(0.78,
(0.09, 0.52)
28
16.86)
0.95)
0.96)
knee)
*Five false positives were from patients with rheumatoid arthritis, one malignancy, and one with elevated ESR prior to primary operation
ESR
(32
mm/hr)
Intraoperative
cultures and
histology
TN
35
51
61
v0.1 03.25.10
Table 25. C-Reactive Protein Results
Level of
Evidence
Author
N
Test
Intraoperative
Cultures
Hip
1.25
(0.4, 3.9)
Histology
Hip
0.93
(0.32,
2.71)
Hip
0.8
(0.26, 2.5)
Hip
3.29
(2.53,
4.28)
Hip
0.94
(0.19,
4.67)
I
Savarino
26
CRP
(0.5mg/dL)
I
Savarino
26
CRP
(0.5mg/dL)
I
Savarino
26
CRP
(0.5mg/dL)
I
Schinsky
201
CRP
(1 mg/dL)
26
CRP
(2 mg/dL)
I
Savarino
Positive
Likelihood
Joint
Ratio
(95% CI)
Reference
Standard
Intraoperative
cultures and
histology
at least 2 of: 1)a
positive
intraoperative
culture (on solid
media) 2)gross
purulence 3)final
histopathological
result consistent
with infection
(average of >10
PMN in the 5
most cellular high
power fields)
Intraoperative
Cultures
Negative
Likelihood
Ratio
(95% CI)
0.89
(0.51,
1.56)
1.04
(0.59,
1.81)
1.12
(0.64,
1.95)
Sensitivity
(95% CI)
Specificity
TP FN FP
(95% CI)
TN
6
10
3
7
4
8
5
9
0.3
(0.07,
0.65)
0.7
(0.35,
0.93)
0.64
(0.35,
0.87)
0.63
(0.35,
0.85)
3
7
6
10
0.08
(0.03,
0.23)
0.95
(0.85,
0.99)
0.71
(0.63,
0.78)
52
3
42
104
1.02
(0.69, 1.5)
0.19
(0.04,
0.46)
0.8
(0.44,
0.97)
3
13
2
8
0.38
(0.15,
0.65)
0.33
(0.1, 0.65)
62
v0.1 03.25.10
Table 25. C-Reactive Protein Results (Continued)
Level of
Evidence
Author
N
I
Savarino
26
I
Savarino
I
Greidanus 151
I
Greidanus 151
I
Fink
26
145
Test
CRP
(2
mg/dL)
CRP
(2
mg/dL)
CRP
(1.0
mg/dL)
CRP
(1.35
mg/dL)
CRP
(1.35
mg/dL)
Reference
Standard
Histology
Intraoperative
cultures and
histology
Cultures –
Intraoperative or
Aspiration
Cultures –
Intraoperative or
Aspiration
Intraoperative
cultures and
histology
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
Hip
4.67
(0.6, 36.29)
0.72
(0.47, 1.1)
0.33
(0.1, 0.65)
0.93
(0.66, 1)
4
8
1
13
Hip
2.4
(0.48,
11.95)
0.8
(0.51, 1.25)
0.88
(0.62,
0.98)
3
7
2
14
Knee
5.5
(3.58, 8.43)
0.08
(0.03, 0.24)
0.83
(0.74, 0.9)
42
3
18
88
Knee
6.9
(4.2, 11.33)
0.1
(0.04, 0.26)
41
4
14
92
Knee
3.81
(2.46, 5.9)
0.34
(0.2, 0.57)
0.3
(0.07,
0.65)
0.93
(0.82,
0.99)
0.91
(0.79,
0.98)
0.73
(0.56,
0.85)
29
11
20
85
0.87
(0.79,
0.93)
0.81
(0.72,
0.88)
TP FN FP TN
63
v0.1 03.25.10
Table 25. C-Reactive Protein Results (Continued)
Level of
Evidence
I
Author
Della
Valle
Test
Reference
Standard
94
CRP
(1
mg/dL)
at least 2 of 3
positive
intraoperative
cultures on solid
media or if 2 of
following: 1)at
least 1 positive
culture 2)final
histopathology
consistent with
infection 3)gross
purulence seen at
time of revision
Intraoperative
cultures and
histology
Intraoperative
cultures and
histology
N
I
Bottner
78
CRP
(1.5
mg/dL)
I
Bottner
78
CRP
(3.2
mg/dL)
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
Knee
3.88
(2.41, 6.25)
0.06
(0.02, 0.25)
0.95
(0.83,
0.99)
0.75
(0.62,
0.86)
39
2
13
40
10.86
(4.67,
25.22)
0.05
(0.01, 0.35)
0.95
(0.76, 1)
0.91
(0.81,
0.97)
20
1
5
52
27.14
(6.93, 106)
0.05
(0.01, 0.33)
0.95
(0.76, 1)
0.96
(0.88, 1)
20
1
2
55
Mixed
(50
hip, 28
knee)
Mixed
(50
hip, 28
knee)
TP FN FP TN
64
v0.1 03.25.10
Table 26. ESR and CRP Results
Level of
Evidence
Author
N
I
Greidanus 151
I
Greidanus 151
I
I
Test
ESR and
CRP –
positive if
both
positive
(22.5/1.35)
ESR and
CRP –
positive if
both
positive
(30/1.0)
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
Cultures –
Intraoperative
or Aspiration
Knee
13.5
(6.53, 27.7)
0.12
(0.05, 0.27)
0.89
(0.76,
0.96)
Cultures –
Intraoperative
or Aspiration
Knee
12.1
(5.83, 25.2)
0.21
(0.12, 0.38)
Reference
Standard
201
ESR and
CRP –
positive if
both
positive
(30/1.0)
At least 2 of:
1)positive
intraoperative
culture (on solid
media) 2)gross
purulence
3)final
histopathology
Hip
4.34
(3.11, 6.04)
Greidanus 151
ESR and
CRP –
positive if
one
positive
(22.5/1.35)
Cultures –
Intraoperative
or Aspiration
Knee
4.22
(2.95, 6.03)
Schinsky
TP FN FP
TN
0.93
(0.87,
0.97)
40
5
7
99
0.8
(0.65,
0.90)
0.93
(0.87,
0.97)
36
9
7
99
0.14
(0.06, 0.26)
0.89
(0.78,
0.96)
0.79
(0.72,
0.86)
49
6
30
116
0.06
(0.01, 0.22)
0.96
(0.85,
0.99)
0.77
(0.68,
0.85)
43
2
24
82
65
v0.1 03.25.10
Table 26. ESR and CRP Results (Continued)
Level of
Evidence
I
I
Test
Reference
Standard
Greidanus 151
ESR and
CRP –
positive
if one
positive
(30/1.0)
Cultures –
Intraoperative or
Aspiration
Schinsky
ESR and
CRP –
positive
if one
positive
(30/1.0)
At least 2 of:
1)positive
intraoperative
culture (on solid
media) 2)gross
purulence 3)final
histopathology
Author
N
201
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
Knee
4.22
(2.95, 6.03)
0.06
(0.01, 0.22)
0.96
(0.84,
0.99)
0.77
(0.68,
0.85)
43
2
24
82
Hip
1.74
(1.51, 2.0)
0
1
(0.94, 1)
0.43
(0.34,
0.51)
55
0
84
62
TP FN FP TN
66
v0.1 03.25.10
Table 27. Radiography Results
Level of
Evidence
I
Author
N
Cyteval 65
Test
Radiograph asymmetric
position of
femoral head
Radiograph bone
abnormalities
(focal or
nonfocal
lucency,
periostitis)
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
Hip
0.52
(0.14, 1.95)
1.23
(0.9, 1.68)
0.17
(0.02,
0.48)
0.68
(0.54, 0.8)
2
10
17
36
Intraoperative
Cultures (≥2)
Hip
1.05
(0.72, 1.51)
0.88
(0.3, 2.57)
0.75
(0.43,
0.95)
0.28
(0.17,
0.42)
9
3
38
15
0.25
(0.05,
0.57)
0.79
(0.66,
0.89)
3
9
11
42
0.5
(0.21,
0.79)
0.17
(0.02,
0.48)
0.49
(0.35,
0.63)
6
6
27
26
1
(0.93, 1)
2
10
0
53
0.67
(0.43,
0.85)
8
2
7
14
Reference
Standard
Intraoperative
Cultures (≥2)
I
Cyteval 65
I
Cyteval 65
Radiograph focal lucency
Intraoperative
Cultures (≥2)
Hip
1.2
(0.4, 3.66)
0.95
(0.66, 1.35)
I
Cyteval 65
Radiograph nonfocal
lucency
Intraoperative
Cultures (≥2)
Hip
0.98
(0.53, 1.83)
1.02
(0.54, 1.91)
I
Cyteval 65
Radiograph periostitis
Intraoperative
Cultures (≥2)
Hip
20.77
(1.06, 407)
0.82
(0.62, 1.06)
Radiograph
Pathological
and Gross
Operative
Findings
Hip
2.4
(1.22, 4.74)
0.3
(0.08, 1.07)
II
Bernay
31
0.8
(0.44,
0.97)
TP FN FP TN
67
v0.1 03.25.10
Table 27. Radiography Results (Continued)
Level of
Evidence
III
III
Author
N
Test
Barrack 69
Radiograph:
complete
radiolucent
line adjacent to
tibial
component
Barrack 69
Radiograph:
gross
loosening
Reference
Standard
Intraoperative
cultures on
solid media,
aspiration
culture
confirmed by
intraoperative
culture in liquid
media, or
intraoperative
histology
Intraoperative
cultures on
solid media,
aspiration
culture
confirmed by
intraoperative
culture in liquid
media, or
intraoperative
histology
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
Knee
1.96
(0.59, 6.56)
0.89
(0.7, 1.13)
0.2
(0.06,
0.44)
0.9
(0.78,
0.97)
4
16
5
44
Knee
0.92
(0.27, 3.11)
1.02
(0.81, 1.27)
0.15
(0.03,
0.38)
0.84
(0.7, 0.93)
3
17
8
41
TP FN FP TN
68
v0.1 03.25.10
Table 27. Radiography Results (Continued)
Level of
Evidence
III
III
Author
N
Barrack 69
Barrack 69
Test
Radiograph:
Knee Society
Grade 3
classification
for
radiolucency
for the tibial
component in
addition to
Grade 1 under
femoral
component
Radiograph:
periostitis
Reference
Standard
Intraoperative
cultures on
solid media,
aspiration
culture
confirmed by
intraoperative
culture in liquid
media, or
intraoperative
histology
Intraoperative
cultures on
solid media,
aspiration
culture
confirmed by
intraoperative
culture in liquid
media, or
intraoperative
histology
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
Knee
2.99
(1.47, 6.1)
0.55
(0.33, 0.91)
0.55
(0.32,
0.77)
0.82
(0.68,
0.91)
11
9
9
40
Knee
1.04
(0.73, 1.47)
0.92
(0.42, 2.01)
0.7
(0.46,
0.88)
0.33
(0.2, 0.48)
14
6
33
16
TP FN FP TN
69
v0.1 03.25.10
Table 28. White Blood Cell Count Results
Level of
Evidence
Test
Reference Standard
Spangehl 202
WBC
(11.0x10^9/L
at least 1 of: 1)open
wound of sinus in
communication with the
joint 2)systemic
infection with pain in the
joint and purulent fluid
within the joint
3)positive result on at
least 3
investigations(ESR>30,
CRP>10, preoperative
aspiration with at least 1
positive culture, frozen
section with
>5PMN/HPF,
intraoperative culture
(>1/3 of cultures
positive)
I
Savarino
26
WBC
(9500/mm^3)
Hip
I
Savarino
26
WBC
(9500/mm^3)
Histology
Hip
I
Savarino
26
WBC
(9500/mm^3)
and histology
Hip
I
Author
N
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
5.57
(1.99,
15.56)
0.83
(0.7, 0.98)
0.2
(0.08,
0.37)
0.96
(0.92,
0.99)
7
28
6
161
1.94
(0.09,
43.5)
3.46
(0.15,
77.86)
4.64
(0.21,
103.9)
0.96
(0.79,
1.16)
0.92
(0.74,
1.14)
0.89
(0.69,
1.14)
0.06
(0, 0.3)
1
(0.69, 1)
1
15
0
10
0.08
(0, 0.38)
1
(0.77, 1)
1
11
0
14
0.1
(0, 0.45)
1
(0.79, 1)
1
9
0
16
Positive
Likelihood
Joint
Ratio
(95% CI)
Hip
Specificity
TP FN FP
(95% CI)
70
v0.1 03.25.10
TN
Table 28. White Blood Cell Count Results (Continued)
Level of
Evidence
I
Author
Pill
Test
Reference Standard
Joint
Positive
Likelihood
Ratio
(95% CI)
WBC
(11000/μL)
at least 1 of 3 criteria:
1)an open wound or
sinus communicating
with the joint 2)
systemic infection with
pain in the hip and
purulent fluid within the
joint 3)positive result on
at least 3 tests (ESR,
CRP, joint aspiration,
intraoperative frozen
section, and
intraoperative culture)
Hip
8.45
(1.77,
40.46)
N
92
Negative
Likelihood
Ratio
(95% CI)
0.78
(0.62, 1)
Sensitivity Specificity
(95% CI) (95% CI)
0.24
(0.08,
0.47)
0.97
(0.9, 1)
TP
5
FN FP
TN
16
69
2
71
v0.1 03.25.10
Level of
Evidence
I
Author
Test
Reference Standard
Joint
WBC
differential
(75%
neutrophils)
wound of sinus in
communication with the
joint 2)systemic
infection with pain in
the joint and purulent
fluid within the joint
least 3
aspiration with at least 1
positive culture, frozen
section with
>5PMN/HPF,
(>1/3 of cultures
positive)
Hip
2.01
(0.96,
4.22)
0.87
(0.72,
1.05)
0.23
(0.1, 0.4)
0.89
(0.83,
0.93)
1.77
(1.17,
2.68)
0.48
(0.24,
0.97)
0.71
(0.48,
0.89)
4.29
(2.38,
7.73)
0.08
(0.01,
0.51)
0.94
(0.71, 1)
N
Spangehl 202
Negative
Likelihood
Ratio
(95% CI)
Positive
Likelihood
Ratio
(95% CI)
I
Bottner
78
WBC
(6200/μL)
and histology
Mixed
(50
hip,
28
knee)
II
Di
Cesare
58
WBC
(11.0x10^9)
and histology
Mixed
(95% CI) (95% CI)
TP
FN FP
TN
8
27
19
148
0.6
(0.46,
0.72)
15
6
23
34
0.78
(0.62,
0.89)
16
1
9
32
72
v0.1 03.25.10
Level of
Evidence
II
II
Author
Trampuz
Bernard
Test
Reference Standard
Joint
Positive
Likelihood
Ratio
(95% CI)
296
WBC count
(10x10^9/L)
at least 1 of: 1)visible
purulence of synovial
fluid or area
surrounding the
prosthesis 2)acute
inflammation on
histopathologic exam of
permanent
periprosthetic tissue
sections (as determined
by the clinical
pathologist) 3)a sinus
tract communicating
with the prosthesis
Mixed
(207
knee,
124
hip)
3.11
(1.51, 6.4)
228
Polynuclear
neutrophil
count
(6000
cells/ml)
Mixed
(167
hip,
63
knee)
2.84
(1.17,
6.92)
N
Negative
Likelihood
Ratio
(95% CI)
(95% CI) (95% CI)
TP
FN FP
TN
0.87
(0.78,
0.97)
0.18
(0.1, 0.29)
0.94
(0.9, 0.97)
13
59
13
211
0.57
(0.44,
0.73)
0.54
(0.47,
0.61)
0.81
(0.58,
0.95)
112
95
4
17
73
v0.1 03.25.10
RECOMMENDATION 3
We recommend joint aspiration of patients being assessed for periprosthetic knee
infections that have abnormal erythrocyte sedimentation rate AND/OR C-reactive protein
results. We recommend that the aspirated fluid be sent for microbiologic culture, synovial
fluid white blood cell count and differential.
Rationale
Our systematic review of the literature suggests that ESR/CRP testing is valuable for
screening (ruling out) of periprosthetic infection with extremely high sensitivity (>90%).
These tests are not, however, specific for diagnosis of periprosthetic infection and may be
elevated with any type of infection or inflammation. Hence, for patients with abnormal
ESR/CRP who are being investigated for periprosthetic infection of the knee, the most
appropriate next test is aspiration of the knee joint.
We recommend that the fluid obtained from the joint be sent for analysis of synovial fluid
white blood cell count, percentage of neutrophils, and also culture for aerobic and
anerobic organisms. Studies suggest either synovial fluid white blood cell count over
1700 cells/μl (range, 1100-3000) or neutrophil percentage greater than 65% (range 64%80%) is highly suggestive of chronic periprosthetic infection.21, 31, 103 However, the
threshold for cell count and neutrophil percentage indicative of acute periprosthetic joint
infection (within six weeks of index arthroplasty) is yet to be determined and the values
and ranges reported above may not be applicable when diagnosing acute periprosthetic
infections.
Supporting Evidence
Two studies with reliable data addressed the diagnostic efficacy of aspiration cultures
among patients being assessed for periprosthetic knee infections.21, 31, 103 Both studies
indicated that this test is a good “rule in” test but only moderately good at ruling out
infection (positive likelihood ratio: 14.2-15.2, negative LR: 0.21-0.29; see Table 32).
Three studies with reliable data addressed synovial fluid white blood cell count and
differential among patients being assessed for periprosthetic knee infections.21, 33 The
studies indicated that both of these tests are good “rule in” and “rule out” tests (synovial
fluid white blood cell count: LR+: 7.6-35.6, LR-: 0.01-0.11; differential: LR+: 6.5-48,
LR-: 0.03-0.05; see Table 33, Table 34).
74
v0.1 03.25.10
SUMMARY OF EVIDENCE
Table 29. Knee Aspiration Summary of Evidence
Test
Number
of Studies
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
Aspiration
Cultures
(range)
2
14.2 – 15.2
0.21 – 0.29
0.73 – 0.80
0.94 – 0.95
Synovial fluid
WBC Count
(range)
3
7.6 – 35.6
0.01 – 0.11
0.91 – 1.0
0.88 – 0.98
Synovial fluid
Neutrophil
Percentage
(range)
3
6.5 – 48.0
0.03 – 0.05
0.95 – 0.98
0.85 – 0.98
75
v0.1 03.25.10
EXCLUDED ARTICLES
Author
Bach, et al.
2002
Title
Total knee arthroplasty infection: significance of delayed aspiration
Does not address
recommendation
Barrack, et al.
1997
The Coventry Award. The value of preoperative aspiration before total knee revision
Not best available
evidence
Duff, et al.
1996
Not best available
evidence
Kersey, et al.
2000
White blood cell counts and differential in synovial fluid of aseptically failed total knee
arthroplasty
Does not address
recommendation
Mason, et al.
2003
The value of white blood cell counts before revision total knee arthroplasty
Not best available
evidence
Parvizi, et al.
2006
Periprosthetic infection: What are the diagnostic challenges?
Not best available
evidence
Parvizi, et al.
2008
Not best available
evidence
Trampuz, et al.
2006
Sonication of explanted prosthetic components in bags for diagnosis of prosthetic joint
infection is associated with risk of contamination
Not best available
evidence
Trampuz, et al.
2007
Sonication of removed hip and knee prostheses for diagnosis of infection
Not best available
evidence
Van den Bekerom,
et al. 2006
The value of pre-operative aspiration in the diagnosis of an infected prosthetic knee: a
retrospective study and review of literature
Not best available
evidence
Virolainen, et al.
2002
Not best available
evidence
76
v0.1 03.25.10
N
Index Test
avoided
described
result(s) reported
Author
Level of
Evidence
STUDY QUALITY
Table 31. Knee Aspiration - Quality
Della Valle
Fink
94
145
Aspiration culture
Aspiration culture
I
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
?
?
●
●
●
●
●
●
Della Valle
94
Synovial fluid WBC
count (>3000/μL)
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
Ghanem
429
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
Trampuz
133
I
?
●
●
●
●
●
●
●
●
●
?
●
●
●
Della Valle
94
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
Ghanem
429
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
Trampuz
133
I
?
●
●
●
●
●
●
●
●
●
?
●
●
●
● = Yes
○ = No
? = Unclear
Synovial fluid WBC
count (>1100/μL)
Synovial fluid WBC
count (>1700/μL)
Synovial fluid WBC
differential (>65%
PMN)
Synovial fluid %
neutrophil (>64%)
Synovial fluid %
neutrophil (>65%)
77
v0.1 03.25.10
STUDY RESULTS
Table 32. Aspiration Culture - Knee
Level of
Evidence
Author
N
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
Test
Reference Standard
Joint
Positive
Likelihood
Ratio
(95% CI)
Knee
14.22
(4.69,
43.12)
0.21
(0.11, 0.39)
0.8
(0.65,
0.91)
0.94
(0.84,
0.99)
3
3
8
50
Knee
15.23
(6.34,
36.58)
0.29
(0.17, 0.48)
0.73
(0.56,
0.85)
0.95
(0.89,
0.98)
29
5
11
100
I
Della
Valle
94
Aspiration
culture on
solid media
At least 2 of 3 positive
intraoperative cultures
on solid media or 2 of
following: 1)at least 1
positive culture 2)final
histopathology
consistent with
infection 3)gross
purulence at revision
I
Fink
145
Aspiration
culture
Intraoperative Cultures
and Histology
TP FP FN
TN
78
v0.1 03.25.10
Table 33. Synovial Fluid White Blood Cell Count
Level of
Evidence
I
Author
Della
Valle
N
94
Test
Reference Standard
Joint
Positive
Likelihood
Ratio
(95% CI)
WBC
(3.0x10^3/μL)
At least 2 of 3
positive
intraoperative
cultures on solid
media or 2 of
following: 1)at least
1 positive culture
2)final
histopathology
consistent with
infection 3)gross
Knee
35.57
(7.34,
172.4)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
0.01
(0, 0.19)
1
(0.91, 1)
0.98
(0.9, 1)
TP FP FN TN
41
0
1
52
79
v0.1 03.25.10
Table 33. Synovial Fluid White Blood Cell Count (Continued)
Level of
Evidence
I
Author
Ghanem
N
Test
WBC
429 (1.1x10^3
/μL)
Reference Standard
Joint
Positive
Likelihood
Ratio
(95% CI)
1)presence of an
abscess or sinus tract
communicating with the
joint space 2)positive
culture of aspirate on
solid medium 3)≥2
positive intraoperative
cultures of the same
organism, or one
positive culture on solid
medium and the
presence of gross
intracapsular purulence
or abnormal histological
findings; when cultures
were negative, infection
was present if had both
grossly purulent fluid
and an abnormal frozen
section (Mirra et al.
criteria)
Knee
7.59
(5.47,
10.55)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
TP
FP FN
TN
0.11
(0.07, 0.17)
0.91
(0.85,
0.95)
0.88
(0.84,
0.92)
146
32
236
15
80
v0.1 03.25.10
Level of
Evidence
I
Author
N
Test
Reference Standard
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
TP
FP FN
TN
at least 1 of the
following criteria:
growth of the same
microorganism in at
least 2 cultures of
synovial fluid or
periprosthetic tissue;
visible synovial fluid
purulence at the time of
7.76
WBC
0.07
0.94
0.88
arthrocentesis or during
(4.54,
32 12
2
87
Knee
Trampuz 133 (1.7x10^3
(0.02, 0.26) (0.8, 0.99) (0.8, 0.94)
surgery; acute
13.28)
/μL)
inflammation on
histopathologic
examination of
permanent
sections; or presence of
a sinus tract
communicating with the
prosthesis
49, 66
Note: Authors of other articles
investigating synovial fluid cell counts who expressed counts in milliliters (ml) were contacted; they confirmed
that the units reported for the cell count in the published report were incorrect. The actual units to indicate periprosthetic infection were microliters
90
(µl) and fall within the limits cited above. Although the units to express cell count differs between published reports, the American College of
90
Rheumatology (ACR) recommends that cell count be expressed as cells/μl.
81
v0.1 03.25.10
Table 34. Synovial Fluid Neutrophil Percentage
Level of
Evidence
I
Author
Della
Valle
N
94
Test
Reference Standard
Joint
Positive
Likelihood
Ratio
(95% CI)
>65%
PMN
At least 2 of 3 positive
intraoperative cultures on
solid media or 2 of
following: 1)at least 1
positive culture 2)final
histopathology consistent
with infection 3)gross
Knee
6.46
(3.41,
12.26)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
TP FP FN TN
0.03
(0, 0.2)
0.98
(0.87, 1)
0.85
(0.72, 0.93)
40
8
1
45
82
v0.1 03.25.10
Table 34. Synovial Fluid Neutrophil Percentage (Continued)
Level of
Evidence
I
Author
Ghanem
N
429
Test
Reference Standard
Joint
Positive
Likelihood
Ratio
(95% CI)
> 64%
Neutrophils
1)presence of an
abscess or sinus tract
communicating with
the joint space
2)positive culture of
aspirate on solid
medium 3)≥2 positive
of the same organism,
or one positive culture
on solid medium and
the presence of gross
intracapsular
purulence or abnormal
histological findings;
when cultures were
negative, infection
was present if had
both grossly purulent
fluid and an abnormal
frozen section (Mirra
et al. criteria)
Knee
18.19
(10.91,
30.33)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
TP
FP FN
TN
0.05
(0.03, 0.1)
0.95
(0.9, 0.98)
0.95
(0.91,
0.97)
153
14
254
8
83
v0.1 03.25.10
Level of
Evidence
I
Author
N
Trampuz 133
Test
Reference Standard
Joint
Positive
Likelihood
Ratio
(95% CI)
> 65%
Neutrophils
at least 1 of the
following criteria:
growth of the same
microorganism in at
least 2 cultures of
synovial fluid or
periprosthetic tissue;
visible synovial fluid
purulence at the time
of arthrocentesis or
during surgery; acute
inflammation on
histopathologic
examination of
permanent
sections; or presence
of a sinus tract
communicating with
the prosthesis
Knee
48.04
(12.17,
189.65)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
TP
0.03
(0, 0.21)
0.97
(0.85, 1)
0.98
(0.93, 1)
33
FP FN
2
1
TN
97
84
v0.1 03.25.10
RECOMMENDATION 4
We recommend a selective approach to aspiration of the hip based on the patient’s
probability of periprosthetic joint infection and the results of the erythrocyte
sedimentation rate (ESR) AND C-reactive protein (CRP). We recommend that the
aspirated fluid be sent for microbiologic culture, synovial fluid white blood cell count and
differential.
Selection of Patients for Hip Aspiration
Probability of
Infection
ESR and CRP
Results
Planned Reoperation
Status
Recommended Test
Higher
+ + or + −
Aspiration
Lower
+ + or + −
Planned
Aspiration or Frozen Section
Lower
++
Not planned
Aspiration
Lower
+−
Not planned
Please see Recommendation 6
Higher or Lower
−−
No further testing
Key for ESR and CRP results
+ + = ESR and CRP test results are abnormal
+ − = either ESR or CRP test result is abnormal
− − = ESR and CRP test results are normal
Rationale
AAOS conducted a systematic review that identified six Level I hip,4, 27, 57, 65, 68, 111 and
one hip and knee study35 on the diagnostic performance of hip aspiration and culture.
(Please see Recommendation 3 for data supporting knee patients.) These studies did not
stratify patients as to whether they were at higher or lower probability for infection, and
all patients underwent re-operation. The indications for patients having an aspiration
varied between studies, with aspiration often a routine part of preoperative investigations.
Our meta-analysis indicated that hip aspiration for culture has a moderate to large ability
to “rule in” infection but a small to moderate ability to “rule out” infection (positive
likelihood ratio 9.8, negative LR 0.33). Based on the meta-analysis, hip aspiration is a
useful test to diagnose periprosthetic hip infection. Therefore, we recommend hip
aspiration in all “higher probability or lower probability” patients undergoing reoperation
of the hip with abnormal ESR and/or CRP results. 4, 27, 35, 57, 65, 68, 111
Given the potential problems with instituting treatment and missing the diagnosis of
infection, “higher probability” patients with an abnormal ESR AND/OR CRP without
planned reoperation should also receive hip aspiration.
There is no reliable evidence, however, on the diagnostic performance of hip aspirations
in patients who are not to undergo reoperation. Possible harms include the possibility of
false positive results, the possibility of the introduction of bacteria into the joint during
the procedure and patient pain and/or discomfort while undergoing the procedure.4 There
85
v0.1 03.25.10
are also concerns about the cost of the procedure.4 Therefore, universal hip aspiration
does not seem indicated. Aspiration is indicated for lower probability hip patients without
planned reoperation only if both ESR AND CRP levels are abnormal. Lower probability
hip arthroplasty patients without planned reoperation who have an abnormal ESR OR
CRP are addressed in Recommendation 6.
We do not recommend that “higher or lower probability” patients with normal ESR and
CRP have hip aspiration prior to planned reoperation.
Supporting Evidence
Six studies of hip patients4, 27, 57, 65, 68, 111 and one study of mixed hip and knee (80%
hip)35 patients, all with reliable data, addressed the diagnostic efficacy of hip aspiration
cultures. Our meta-analysis of these studies indicated that this test is a good “rule in”
test, but not as good at ruling out infection (LR+: 9.8, LR-: 0.33; see Figure 10). The
indications for patients having an aspiration varied between studies, with aspiration often
a routine part of preoperative investigations. Two studies reported that patients were off
antibiotics for at least two weeks prior to aspiration.4, 35 Three studies reported injecting
saline for re-aspiration,35, 68, 111 while three studies reported not doing so.4, 27, 57
Two studies of hip patients with reliable data addressed synovial fluid white blood cell
count and differential.96, 99 The data from these studies indicated that synovial fluid white
blood cell count is a good “rule in” and possibly a good “rule out” test (LR+: 12-55, LR-:
0.18-0.65; see Figure 11). The higher threshold used in one study99 may account for its
higher negative likelihood ratio (0.65). Neutrophil percentage (both studies used an 80%
threshold) was a moderately good “rule in” and “rule out” test (LR+: 4.8-5.9, LR-: 0.130.22; see Figure 12).
None of the results presented includes data based on the use of diagnostic arthrography.
SUMMARY OF EVIDENCE
Table 35. Aspiration Summary of Evidence
Test
Number
of Studies
Positive
Likelihood
Ratio
(95% CI)
Aspiration
9.8
Cultures
7
(5.4,
17.9)
(I2=0%)
Synovial fluid
2
12.2 – 55.4
WBC Count
(range)
Synovial fluid
Neutrophil
2
4.8 – 5.9
Percentage
(range)
*Range presented when fewer than four studies
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
0.33
(0.18, 0.60)
0.69
(0.50, 0.84)
0.93
(0.89, 0.95)
0.18 – 0.65
0.36 – 0.84
0.93 – 0.99
0.13 – 0.22
0.82 – 0.89
0.83 – 0.85
86
v0.1 03.25.10
EXCLUDED ARTICLES
Author
Ali, et al.
2006
Title
Accuracy of joint aspiration for the preoperative diagnosis of infection in total hip
arthroplasty
Not best available
evidence
Bernard, et al.
2004
Value of preoperative investigations in diagnosing prosthetic joint infection: retrospective
cohort study and literature review
Not best available
evidence
Buchholz, et al.
1981
Management of deep infection of total hip replacement
Not best available
evidence
Cheung, et al.
1997
The role of aspiration and contrast-enhanced arthrography in evaluating the uncemented
hip arthroplasty
Not best available
evidence
Chryssikos, et al.
2008
FDG-PET imaging can diagnose periprosthetic infection of the hip
Not best available
evidence
Dussault, et al.
1977
Radiologic diagnosis of loosening and infection in hip prostheses
Insufficient Data
Fehring, et al.
1996
Aspiration as a guide to sepsis in revision total hip arthroplasty
Not best available
evidence
Gelman,
1976
Arthrography in total hip prosthesis complications
Case
report/commentary
Gould, et al.
1990
Role of routine percutaneous hip aspirations prior to prosthesis revision
Not best available
evidence
Guercio, et al.
1990
Arthrography of the prosthesetized painful hip: the importance of imaging and functional
testing
Does not address
recommendation
Itasaka, et al.
2001
Not best available
evidence
Johnson, et al.
1988
Detection of occult infection following total joint arthroplasty using sequential technetium99m HDP bone scintigraphy and indium-111 WBC imaging
Not best available
evidence
87
v0.1 03.25.10
Author
Kraemer, et al.
1993
Title
Bone scan, gallium scan, and hip aspiration in the diagnosis of infected total hip
arthroplasty
Not best available
evidence
Levitsky, et al.
1991
Evaluation of the painful prosthetic joint. Relative value of bone scan, sedimentation rate,
and joint aspiration
Not best available
evidence
Lieberman, et al.
1993
Evaluation of painful hip arthroplasties. Are technetium bone scans necessary?
Not best available
evidence
Lyons, et al.
1985
Evaluation of radiographic findings in painful hip arthroplasties
Not best available
evidence
Magnuson, et al.
1988
In-111-labeled leukocyte scintigraphy in suspected orthopedic prosthesis infection:
comparison with other imaging modalities
Not best available
evidence
Maus, et al.
1987
Arthrographic study of painful total hip arthroplasty: refined criteria
Insufficient Data
McLaughlin, et al.
1977
Evaluation of the painful hip by aspiration and arthrography
Insufficient Data
Muller, et al.
2008
Not best available
evidence
Murray, et al.
1975
Arthrography for the assessment of pain after total hip replacement. A comparison of
arthrographic findings in patients with and without pain
<25 patients
O'Neill, et al.
1984
Failed total hip replacement: assessment by plain radiographs, arthrograms, and aspiration
of the hip joint
Not best available
evidence
Phillips, et al.
1983
Efficacy of preoperative hip aspiration performed in the radiology department
Not best available
evidence
Pons, et al.
1999
Not best available
evidence
88
v0.1 03.25.10
Author
Roberts, et al.
1992
Title
Diagnosing infection in hip replacements. The use of fine-needle aspiration and
radiometric culture
Not best available
evidence
Salenius, et al.
1979
Arthrography of the hip in the diagnosis of postoperative painful conditions after total hip
replacement
Does not address
recommendation
Salvati, et al.
1971
Arthrography for complications of total hip replacement. A review of thirty-one
arthrograms
Insufficient Data
Somme, et al.
2003
Contribution of routine joint aspiration to the diagnosis of infection before hip revision
surgery
Not best available
evidence
Taylor, et al.
1995
Fine needle aspiration in infected hip replacements
Not best available
evidence
Teller, et al.
2000
Sequential indium-labeled leukocyte and bone scans to diagnose prosthetic joint infection
Not best available
evidence
Tigges, et al.
1993
Hip aspiration: a cost-effective and accurate method of evaluating the potentially infected
hip prosthesis
Not best available
evidence
89
v0.1 03.25.10
result(s) reported
I
I
I
I
I
I
I
I
I
described
Aspiration culture
aspiration (initial)
aspiration (repeat)
Aspiration culture
Aspiration culture
Aspiration culture
Aspiration culture
Aspiration culture
Aspiration culture
291
260
31
57
54
156
41
71
273
Barrack
Barrack
Barrack
Eisler
Glithero
Lachiewicz
Malhotra
Mulcahy
Williams
avoided
Level of
Evidence
Index Test
N
Author
● = Yes
○ = No
? = Unclear
STUDY QUALITY
Table 37. Aspiration - Quality
●
●
●
?
●
●
?
?
?
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
?
?
?
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
?
?
?
●
●
?
?
?
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
90
v0.1 03.25.10
Index Test
avoided
described
result(s) reported
N
Level of
Evidence
Author
● = Yes
○ = No
? = Unclear
Table 37. Aspiration – Quality (Continued)
Schinsky
201
Synovial fluid WBC
count (>4200/μl)
I
●
●
●
●
●
●
●
?
●
●
?
●
●
●
Spangehl
183
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
Schinsky
201
I
●
●
●
●
●
●
●
?
●
●
?
●
●
●
Spangehl
181
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
Synovial fluid WBC
count (>50000/μL)
Synovial fluid WBC
differential (>80%
PMN)
Synovial fluid %
neutrophils (>80%)
91
v0.1 03.25.10
STUDY RESULTS
Figure 10. Hip Aspiration Cultures Results - Meta-Analysis
StudyId
StudyId
Glithero
Glithero
Barrack
Barrack
Malhotra
Malhotra
Eisler
Eisler
Mulcahy
Mulcahy
Williams
Williams
Lachiewicz
Lachiewicz
COMBINED
COMBINED
1
2
5 10
.1 .2
.5
1
DLR NEGATIVE
DLR POSITIVE
92
v0.1 03.25.10
Figure 11. Synovial Fluid WBC Count Results - Likelihood Ratios (Hip and Knee)
StudyId
StudyId
Ghanem (knee)- 1100/uL
Ghanem (knee) - 1100/uL
Trampuz (knee) - 1700/uL
Trampuz (knee) - 1700/uL
Della Valle (knee)- 3000/uL
Della Valle (knee) - 3000/uL
Schinsky (hip) - 4200/uL
Schinsky (hip) - 4200/uL
Spangehl (hip)- 50000/uL
Spangehl (hip) - 50000/uL
1 2 510
.1.2
.5
1
DLR NEGATIVE
DLR POSITIVE
Figure 12. Neutrophil Percentage Results – Likelihood Ratios (Hip and Knee)
StudyId
StudyId
Della Valle (knee)
Della Valle (knee)
Trampuz (knee)
Trampuz (knee)
Ghanem (knee)
Ghanem (knee)
Schinsky (hip)
Schinsky (hip)
Spangehl (hip)
Spangehl (hip)
1
2
5
10
.1 .2
DLR POSITIVE
.5
1
DLR NEGATIVE
93
v0.1 03.25.10
Table 38. Aspiration Culture - Hip
Level of
Evidence
Author
N
Test
I
Barrack 291
Aspiration
culture
I
Barrack 260
Aspiration
(initial)
I
Barrack
Aspiration
(repeat)
31
Reference Standard
Correlation between
and histology; the
appearance of the
tissue
intraoperatively; and
the clinical course
Correlation between
and histology; the
appearance of the
tissue
the clinical course
Correlation between
and histology; the
appearance of the
tissue
the clinical course
Joint
Positive
Likelihood
Ratio (95%
CI)
Negative
Likelihood
Ratio (95%
CI)
Sensitivity
(95% CI)
Hip
5.11
(2.81, 9.3)
0.45
(0.21, 0.97)
0.6
0.88
(0.26, 0.88) (0.84, 0.92)
6
33
4
248
Hip
4
(1.42, 11.23)
0.57
(0.21, 1.52)
0.5
0.88
(0.07, 0.93) (0.83, 0.91)
2
33
2
224
Hip
16.67
(2.25,
123.39)
0.35
(0.11, 1.08)
0.67
(0.22, 0.96)
4
1
2
24
Specificity
(95% CI)
0.96
(0.8, 1)
TP FP FN
TN
94
v0.1 03.25.10
Table 38. Aspiration Culture (Continued)
Level of
Evidence
Author
N
I
Eisler
57
I
I
I
Test
Reference
Standard
Joint
Aspiration
culture
Intraoperative
Cultures
Hip
Positive
Likelihood
Ratio (95%
CI)
2.16
(0.12, 39.05)
Negative
Likelihood
Ratio (95%
CI)
0.94
(0.7, 1.27)
31.32
(4.51, 217)
Sensitivity
(95% CI)
Specificity
(95% CI)
0
(0, 0.6)
0.96
(0.87, 1)
0
2
4
51
0.11
(0.03, 0.4)
0.89
(0.67, 0.99)
0.97
(0.85, 1)
17
1
2
34
TP FP FN
TN
54
Aspiration
culture
Intraoperative
Cultures
Mixed
(43
hip, 11
knee)
Lachiewicz 156
Aspiration
culture
Intraoperative
Cultures or
Gross
Purulence
Hip
27.47
(10.34,
73.01)
0.15
(0.06, 0.38)
0.85
(0.66, 0.96)
0.97
(0.92, 0.99)
23
4
4
125
41
Aspiration
culture
Histology
Hip
4.74
(1.29, 17.42)
0.61
(0.34, 1.11)
0.44
(0.14, 0.79)
0.91
(0.75, 0.98)
4
3
5
29
Intraoperative
Cultures and
Histology
Hip
7.56
(3.08, 18.58)
0.34
(0.17, 0.71)
0.69
(0.41, 0.89)
0.91
(0.8, 0.97)
11
5
5
50
Intraoperative
Cultures
Hip
12.47
(7.28, 21.37)
0.21
(0.13, 0.34)
0.8
(0.69, 0.89)
0.94
(0.89, 0.97)
57
13
14
189
Glithero
Malhotra
I
Mulcahy
71
Aspiration
culture
I
Williams
273
Aspiration
culture
95
v0.1 03.25.10
Table 39. Synovial Fluid White Blood Cell Count
Level of
Evidence
I
I
I
Author
N
Test
Schinsky 201
WBC
(4.2x10^3/μl)
Schinsky
79
WBC
(3.0x10^3/μl),
among
patients with
elevated ESR
and CRP
79
WBC
(9.0x10^3/μl),
among
patients with
elevated ESR
and CRP
Schinsky
Reference
Standard
At least 2 of: 1)a
positive
intraoperative
culture (on solid
media) 2)gross
purulence 3)final
histopathology
At least 2 of: 1)a
positive
intraoperative
culture (on solid
media) 2)gross
purulence 3)final
histopathology
At least 2 of: 1)a
positive
intraoperative
culture (on solid
media) 2)gross
purulence 3)final
histopathology
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
Hip
12.21
(6.64,
22.46)
0.18
(0.1, 0.32)
0.84
(0.71,
0.92)
Hip
8.98
(3.06, 26.4)
0.11
(0.05, 0.26)
Hip
8.16
(2.77, 24.1)
0.20
(0.11, 0.37)
TP FP FN
TN
0.93
(0.88,
0.97)
46
10
9
136
0.90
(0.78,
0.97)
0.90
(0.73,
0.98)
44
3
5
27
0.82
(0.68,
0.91)
0.90
(0.73,
0.98)
40
3
9
27
96
v0.1 03.25.10
Level of
Evidence
Author
N
I
Schinsky
60
I
Schinsky
60
Test
Reference Standard
WBC
(3.0x10^3/μl),
among
patients with
elevated ESR
or CRP, not
both
WBC
(9.0x10^3/μl),
among
patients with
elevated ESR
or CRP, not
both
At least 2 of: 1)a
positive
intraoperative
culture (on solid
media) 2)gross
purulence 3)final
histopathology
At least 2 of: 1)a
positive
intraoperative
culture (on solid
media) 2)gross
purulence 3)final
histopathology
Positive
Likelihood
Joint
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
TP FP FN
TN
Hip
6.43
(2.95, 14)
0.19
(0.03,
1.15)
0.83
(0.36, 1)
0.87
(0.75,
0.95)
5
7
1
47
Hip
86.4
(5.3, 1402)
0.22
(0.05,
0.89)
0.83
(0.36, 1)
1
(0.93, 1)
5
0
1
54
97
v0.1 03.25.10
Level of
Evidence
I
Author
N
Spangehl 183
Test
Reference Standard
WBC
(5.0x10^4/μL)
wound of sinus in
communication with
the joint 2)systemic
infection with pain
in the joint and
purulent fluid within
the joint 3)positive
result on at least 3
investigations(ESR,
CRP, preoperative
aspiration, frozen
section,
intraoperative
cultures
Positive
Likelihood
Joint
Ratio
(95% CI)
Hip
55.36
(7.37,
415.6)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
0.65
(0.49,
0.85)
0.36
(0.19,
0.56)
0.99
(0.96, 1)
TP FP FN
TN
10
154
1
18
98
v0.1 03.25.10
Table 40. Synovial Fluid Neutrophil Percentage
Level of
Evidence
I
I
Author
N
Schinsky 201
Schinsky
79
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
TP FP FN
TN
>80%
PMN
At least 2 of:
1)positive
intraoperative
culture (on solid
media) 2)gross
purulence 3)final
histopathology
Hip
4.78
(3.27, 6.97)
0.22
(0.12, 0.39)
0.82
(0.69, 0.91)
0.83
(0.76, 0.89)
45
25
10
121
>80%
PMN,
among
patients
with
elevated
ESR and
CRP
At least 2 of:
1)positive
intraoperative
culture (on solid
media) 2)gross
purulence 3)final
histopathology
Hip
8.78
(2.98, 25.8)
0.14
(0.06, 0.29)
0.88
(0.75, 0.95)
0.90
(0.73, 0.98)
43
3
6
27
Test
Reference
Standard
99
v0.1 03.25.10
Level of
Evidence
I
Author
N
Spangehl 181
Test
Reference Standard
Joint
Positive
Likelihood
Ratio
(95% CI)
>80%
Neutrophils
wound of sinus in
communication with
least 3 investigations
(ESR, CRP,
preoperative
aspiration, frozen
section, intraoperative
cultures
Hip
5.94
(3.99, 8.84)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
TP FP FN
TN
0.13
(0.04, 0.37)
0.89
(0.72,
0.98)
0.85
(0.78, 0.9)
25
130
23
3
100
v0.1 03.25.10
RECOMMENDATION 5
We suggest a repeat hip aspiration when there is a discrepancy between the probability of
periprosthetic joint infection and the initial aspiration culture result.
Rationale
A repeat hip aspiration is suggested when there is a discrepancy between the clinical
probability of infection and the result of the initial aspiration culture.
One Level I study addressed this recommendation. This study examined performing a
repeat hip aspiration in 28 patients because their initial aspiration result conflicted with
the clinical suspicion for periprosthetic infection.4 This report suggests that repeat
aspiration of the hip be considered when 1) the clinical probability of infection is low but
the initial aspiration culture result is positive, or 2) if the clinical probability of infection
is high and the initial aspiration culture result is negative (see Supporting Evidence
below, for details).
The results of additional tests will raise or lower the probability of periprosthetic
infection. The study on which this recommendation is based predated the more routine
use and acceptance of synovial fluid white blood cell count and differential. Thus,
depending on the results of the synovial fluid white blood cell count and differential, as
well as the ESR and CRP, the diagnosis or exclusion of periprosthetic infection may be
apparent and repeat aspiration may not be necessary.
Supporting Evidence
One study4 with reliable data performed repeat aspiration in 28 patients because the
initial aspiration results contradicted clinical suspicions: 25 patients had a positive initial
culture but no clinical or radiographic indication of infection while 3 patients had either a
negative culture or a culture positive for S. epidermidis only but infection was clinically
suspected. 24 of the 25 with a positive initial culture had a negative repeat aspiration; the
other had a false positive repeat aspiration. The three patients with suspected infection
each had two repeat aspirations. The second aspiration was negative in two and positive
in one, while the third aspiration was positive in all three. Repeat aspiration was
attempted but no fluid was obtained in five additional hips. The results are presented in
Table 43.
101
v0.1 03.25.10
EXCLUDED ARTICLES
Author
Fehring, et al.
1996
Title
<25 patients
Glithero, et al.
1993
White cell scans and infected joint replacements. Failure to detect chronic infection
<25 patients
Lachiewicz, et al.
1996
Aspiration of the hip joint before revision total hip arthroplasty. Clinical and laboratory
factors influencing attainment of a positive culture
<25 patients
Somme, et al.
2003
Contribution of routine joint aspiration to the diagnosis of infection before hip revision
surgery
<25 patients
Spangehl, et al.
1999
Prospective analysis of preoperative and intraoperative investigations for the diagnosis of
infection at the sites of two hundred and two revision total hip arthroplasties
<25 patients
Taylor, et al.
1995
Fine needle aspiration in infected hip replacements
<25 patients
102
v0.1 03.25.10
result(s) reported
I
I
described
aspiration (initial)
aspiration (repeat)
260
31
Barrack
Barrack
avoided
Level of
Evidence
Index Test
N
Author
● = Yes
○ = No
? = Unclear
STUDY QUALITY
Table 42. Repeat Aspiration - Quality
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
?
?
●
●
?
?
●
●
●
●
●
●
STUDY RESULTS
Table 43. Repeat Aspiration Results
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio (95%
CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
TP
FP
FN
TN
Initial
Aspiration
Hip
4
(1.42, 11.23)
0.57
(0.21, 1.52)
0.5
(0.07, 0.93)
0.88
(0.83,
0.91)
2
33
2
224
Repeat
Aspiration
Hip
16.67
(2.25, 123.4)
0.35
(0.11, 1.08)
0.67
(0.22, 0.96)
0.96
(0.8, 1)
4
1
2
24
Level of
Evidence
Author
N
Test
I
Barrack
260
I
Barrack
31
103
v0.1 03.25.10
RECOMMENDATION 6
In the absence of reliable evidence, it is the opinion of the work group that lower
probability hip arthroplasty patients without planned reoperation who have abnormal
erythrocyte sedimentation rates OR abnormal C-reactive protein levels be re-evaluated
for infection within three months. We are unable to recommend specific diagnostic tests
at the time of this follow-up.
Rationale
In the opinion of the work group, the possible harms associated with performing hip
aspiration need to be weighed when conflicting erythrocyte sedimentation rates OR
abnormal C-reactive protein levels are found in the patient. Lower probability hip
arthroplasty patients without planned reoperation who have an abnormal ESR OR CRP
are to be re-evaluated within three months. If the patient is asymptomatic, further testing
may not be necessary.
Hip aspiration is a useful test to diagnose periprosthetic hip infection in patients who
have a higher probability of infection and abnormal ESR or CRP as referenced in
Recommendation 4. However, possible harms of joint aspiration include the possibility of
false positive results, the possibility of the introduction of bacteria into the joint during
the procedure and patient pain and/or discomfort while undergoing the procedure.4 There
are also concerns about the cost of the procedure.4 Lower probability hip arthroplasty
patients without planned reoperation who have an abnormal ESR OR CRP are to be reevaluated within three months.
There is insufficient evidence to address whether further observation alone, diagnostic
testing, or both can be recommended based on lack of available evidence to address the
recommendation.
Hip arthroplasty patients at a lower probability of infection who have an isolated
elevation in ESR OR CRP levels but without other objective or subjective evidence of
periprosthetic infection include patients who have a known unrelated cause for this
elevation. Such patients may not require future observation. However, this patient group
also includes the low-grade subclinical infection or early onset periprosthetic infection
that has not fully declared itself.
Because of the often insidious nature of periprosthetic infection, the orthopedic surgeon
will need to use clinical judgment in each individual case. Options to consider include
simple future observation with repeat ESR and CRP testing and reentering the patient
into the diagnostic algorithm versus attempting to immediately establish the presence or
absence of periprosthetic infection with additional testing. Discussion of available
diagnostic procedures applicable to the individual patient relies on mutual
communication between the patient and physician, weighing the potential risks and
benefits for that patient. The ultimate judgment regarding any specific procedure or
treatment must be made in light of all circumstances presented by the patient.
104
v0.1 03.25.10
Supporting Evidence
We found no data specific to this patient population.
105
v0.1 03.25.10
RECOMMENDATION 7
In the absence of reliable evidence, it is the opinion of the work group that a repeat knee
aspiration be performed when there is a discrepancy between the probability of
periprosthetic joint infection and the initial aspiration culture result.
Rationale
It was the consensus of the work group that data be extrapolated from recommendation 5
for periprosthetic knee infections even though there was no reliable evidence pertaining
to the utility of a repeat knee aspiration. (The available study5 enrolled too few patients to
be reliable.)
It is the opinion of the work group that repeat aspiration be performed when 1) the
clinical probability of infection is low but the initial aspiration culture result is positive,
or 2) if the clinical probability of infection is high and the initial aspiration culture result
is negative.
The final decision on whether to perform a repeat knee aspiration may also be influenced
by other factors. The results of additional tests will raise or lower the probability of
periprosthetic infection. Thus, depending on the results of ESR and CRP, as well as the
synovial fluid white blood cell count and differential, the diagnosis or exclusion of
periprosthetic infection may be more apparent and repeat aspiration may not be
necessary.
Supporting Evidence
No studies met the inclusion criteria for this recommendation.
EXCLUDED ARTICLES
Table 44. Excluded Article - Recommendation 7
Author
Title
Reason for
Exclusion
Barrack, et al.
1997
The Coventry Award. The value of preoperative
aspiration before total knee revision
<25 patients
106
v0.1 03.25.10
RECOMMENDATION 8
We suggest patients be off of antibiotics for a minimum of 2 weeks prior to obtaining
intra-articular culture.
Rationale
Culture “yield” (isolation of infecting organism) is lower in patients who are receiving or
have recently (within two weeks) received antibiotics.105 This may be because elution of
antibiotics into the joint fluid interferes with isolating the infecting organism by culture.
Although, the exact “antibiotic-free” time needed to allow ”wash-out” of antibiotics from
systemic circulation and the joint is not known, the work group has accepted two weeks
as the minimum time required. One study showed that the false negative rate of cultures
was significantly higher in patients who received antibiotics within two weeks of
aspiration of a joint.105
Supporting Evidence
One included study with reliable data addressed whether antibiotic therapy decreases the
sensitivity of intraoperative cultures in diagnosing periprosthetic infection.105 The group
of patients who had received antimicrobial therapy within 14 days of surgery had a
statistically significantly higher rate of false-negative culture results than those who had
not. In this study, a positive result was defined as growth from at least two specimens.
107
v0.1 03.25.10
EXCLUDED ARTICLES
Author
Barrack, et al.
1997
Title
<25 patients/arm
Datz, et al.
1986
Effect of antibiotic therapy on the sensitivity of indium-111-labeled leukocyte scans
Not relevant - not
specific to pji
Spangehl, et al.
1999
<25 patients/arm
Spangehl, et al.
1999
The role of intraoperative gram stain in the diagnosis of infection during revision total hip
arthroplasty
<25 patients/arm
Trampuz, et al.
2006
<25 patients
108
v0.1 03.25.10
Author
N
Index Test
Level of
Evidence
Differential verification bias avoided
described
result(s) reported
STUDY QUALITY
Table 46. Preoperative Antibiotic Therapy - Quality
Trampuz
78
Intraoperative
Cultures (≥2)
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
● = Yes
○ = No
? =Unclear
STUDY RESULTS
Table 47. Preoperative Antibiotics and False-Negative Cultures
Level of
Evidence
I
Author
Trampuz
N
79
Joint
Mixed
Reference Standard
False Negatives
Risk Ratio
pvalue
At least 1 of: 1)visible purulence of synovial
fluid or area surrounding the prosthesis
2)acute inflammation on histopathologic
exam of permanent periprosthetic tissue
sections 3)a sinus tract communicating with
the prosthesis
Antibiotics within 14 days: 55%
No antibiotics within 14 days: 23%
2.38
(1.26,
4.51)
0.004
109
v0.1 03.25.10
RECOMMENDATION 9
Nuclear imaging (Labeled leukocyte imaging combined with bone or bone marrow
imaging, FDG-PET imaging, Gallium imaging, or labeled leukocyte imaging) is an
option in patients in whom diagnosis of periprosthetic joint infection has not been
established and are not scheduled for reoperation.
Strength of Recommendation: Weak
Rationale
The information presented throughout this guideline shows that there is no single
preoperative investigation that can reliably diagnose an infection. Diagnosis usually
depends on the combined use of numerous tests. Recognizing subclinical infections
before revision surgery is, therefore, a major concern.
Patients in whom diagnosis of infection has not been established includes patients with a
higher probability of infection who have abnormal ESR and/or CRP levels, but whose
aspiration results are inconclusive (i.e., fluid cannot be obtained from the joint or culture
and cell count results disagree).
The studies included for this recommendation, while of Level I and Level II quality, were
not specific to patients not scheduled for reoperation, so the work group downgraded the
strength of the recommendation from moderate to weak.
In addition, imaging studies may require special expertise and consultation with the
imaging provider.
Technetium-99- or Indium-111-labeled-Leukocyte Imaging
Four included studies indicated that a Tc-99-labeled white blood cell scan was possibly a
useful “rule in” test (range of positive LR:1.4-22),35, 93, 97, 101 while five included In-111
studies indicated that it was possibly useful as both a “rule in” and “rule out” test (range
of positive LR: 2-14; range of negative LR: 0.03-0.63).35, 46, 63, 85, 87
Combined labeled-Leukocyte/Bone Imaging
Three included studies of combined Tc-99 bone scans and In-111 white blood cell scans
also indicated the possible utility of these tests for confirming and excluding infection
(range of positive LR:3-18, range of negative LR: 0.12- 0.47).46, 95, 102 One study of
combined Tc-99 bone scans and Tc-99 white blood cell scans produced similar results
(positive LR: 6, negative LR: 0.44).84
Combined labeled-Leukocyte/Bone Marrow Imaging
The four included studies of combined leukocyte/bone marrow imaging indicated that the
test may be a good “rule in” and “rule out” test, but the results varied between studies
(range of positive LR: 9.8-45, range of negative LR: 0.02- 0.34).47, 60, 67, 97
110
v0.1 03.25.10
Gallium-67 Imaging
Two included studies indicated that it may be a good “rule in” test but the ability of this
test to rule out infection was unclear (range of positive LR: 24-111, range of negative LR:
0.07-0.62).55, 88
FDG-PET Imaging
Three included studies of FDG-PET imaging indicated that the test is possibly good at
both ruling in and ruling out infection but, again, the results varied between studies
(range of positive LR: 11-19; range of negative LR: 0.16-0.66).15, 20, 60
Technetium-99m Bone Imaging
The three included studies of triple-phase Tc-99m bone scintigraphy varied in their
estimates of the test’s diagnostic efficacy, limiting the ability to determine whether the
test is effective at either confirming or excluding infection (range of positive LR: 2-8,
range of negative LR: 0.1-0.8).9, 58, 73 One included study of two-phase Tc-99m bone
scintigraphy provided no evidence of diagnostic efficacy (positive LR: 1.0, negative LR:
1.7).97 Based on these studies, triple-phase Tc-99m bone imaging may be possibly useful;
however, there is no consistent evidence of diagnostic benefit. Therefore more study is
needed.
Computed Tomography (CT) and Magnetic Resonance Imaging, MRI
Please refer to Recommendation 10 for information concerning these modalities.
Supporting Evidence
The indications for performing nuclear imaging varied between studies, and thus the
results presented here are not specific to patients not scheduled for reoperation. This
reduces the applicability of these studies’ findings and, hence, the strength of
recommendation.
Technetium-labeled leukocyte imaging: We included four studies: one study of mixed hip
and knee patients with reliable data (could separate out according to site but less than 25
knee patients), two studies of hip patients with moderately reliable data, and one study of
mixed patients with moderately reliable data.35, 93, 97, 101 Estimates of the positive
likelihood ratio ranged from 1.4-22, while estimates of the negative LR ranged from
0.06-0.52. Meta-analysis of these studies indicated between-study heterogeneity (I2 =
97%), limiting the ability to draw conclusions. The results are presented in Table 51.
Indium-labeled leukocyte imaging: We included five studies: one of hip patients, one of
knee patients, and three of mixed patients.35, 46, 63, 85, 87 All but one study contained
moderately reliable data. Meta-analysis of these studies indicated between-study
heterogeneity (I2 = 85%), as the positive likelihood ratio point estimates ranged from 214 and the negative LR ranged from 0.03-0.63. The results are presented in Table 52.
111
v0.1 03.25.10
Combined labeled-leukocyte/bone imaging: We included three Tc-99m HDP/In-111
leukocyte studies of mixed patients (could separate hip from knee patients in one) with
reliable data in one study and moderately reliable data in the other two.46, 95, 102 We also
included one Tc-99m MDP/Tc-99 leukocyte study of hip patients with moderately
reliable data.82 Each study found statistically significant results for positive and negative
likelihood ratios (range of positive LR:3-18, range of negative LR: 0.12- 0.47). Metaanalysis of these four studies indicates small or moderate diagnostic effects (positive LR:
5.8, negative LR: 0.32). The results are presented in Table 53.
Combined labeled-leukocyte/bone marrow imaging: We included three studies of mixed
patients with reliable data in one study and moderately reliable data in the other two.47, 60,
97
We also included one study of hip patients with moderately reliable data.67 Each study
found statistically significant results for positive and negative likelihood ratios (range of
positive LR: 9.8-45, range of negative LR: 0.02- 0.34). Meta-analysis of these studies
indicated between-study heterogeneity (I2 = 55%), limiting the ability to draw
conclusions. The results are presented in Table 54.
Gallium imaging: We included two studies with moderately reliable data.55, 88 Both
positive and negative likelihood ratios were statistically significant and suggest that
gallium imaging may be a good “rule in” test (range of positive LR: 24-111), but its
usefulness at ruling out infection is unclear (negative LR range: 0.07 – 0.62). The results
are presented in Table 55.
FDG-PET: We included one study of hip patients with reliable data and two studies of
mixed hip and knee patients with moderately reliable data.15, 20, 60 All three studies found
a statistically significant result for positive likelihood ratios, and two of the three found a
statistically significant result for negative likelihood ratios. The results are presented in
Table 56.
Tc-99m bone imaging: We included two studies of hip patients (one with reliable data,
one with moderately reliable data) and two studies of mixed hip and knee patients (both
with reliable data).9, 58, 73, 97 Three of the studies investigated triple-phase bone imaging, 9,
58, 73
while one investigated two-phase bone imaging.97 For triple-phase bone imaging,
estimates of the positive likelihood ratio ranged from 2.3-8.5 and estimates of the
negative likelihood ratio ranged from 0.1-0.8, indicating possible, but inconsistent, smallto-moderate diagnostic benefit. The two-phase bone imaging results (positive LR of 1.0
and a negative LR of 1.7) indicated a lack of diagnostic benefit. The results are presented
in Table 57.
Other imaging: We included one additional study with reliable data of antigranulocyte
antibody scintigraphy among knee patients53 and one study with moderately reliable data
of nanocolloid scintigraphy among hip patients.9 The diagnostic effects were significant
but with wide confidence intervals for both studies. The results are presented in Table 58.
112
v0.1 03.25.10
SUMMARY OF EVIDENCE
Table 48. Nuclear Imaging Summary of Evidence
Number
of
Studies
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
Tc-labeled WBC
imaging (range)
4
1.39 – 22.0
0.06 – 0.52
0.5 - 1
0.31 - 1
In-labeled WBC
imaging (range)
5
1.9 – 14.0
0.03 – 0.63
0.38 - 1
0.5 - 1
4
5.8
(3.1, 10.8)
0.32
(0.20, 0.50)
0.72
(0.59, 0.82)
0.88
(0.79, 0.93)
4
9.8 – 45.5
0.02 – 0.34
0.67 - 1
0.91 – 1
Gallium imaging
(range)
2
24.4 -111
0.07 – 0.62
0.38 – 0.95
1
FDG-PET
imaging (range)
3
11.4 – 19.2
0.16 – 0.66
0.36 – 0.85
0.93 – 1
3
2.33 – 8.53
0.13 - 0.78
0.33 – 0.88
0.76 – 0.90
1
0.99
(0.94, 1.05)
1.72
(0.04, 84.59)
1
(0.88, 1)
0
(0, 0.07)
Test
Combined bone/
labeled WBC
imaging
Combined bone
marrow/labeled
WBC imaging
(range)
Triple-phase
bone imaging
(range)
Dual-phase bone
imaging
*Range presented when fewer than four studies or when meta-analysis indicated heterogeneity
113
v0.1 03.25.10
EXCLUDED ARTICLES
Author
Achong, et al.
1994
Title
The computer-generated bone marrow subtraction image: a valuable adjunct to combined
In-111 WBC/Tc-99m in sulfur colloid scintigraphy for musculoskeletal infection
Not relevant - not
specific to pji
Aliabadi, et al.
1989
Cemented total hip prosthesis: radiographic and scintigraphic evaluation
Not best available
evidence
Bauer, et al.
1973
85Sr radionuclide scintimetry in infected total hip arthroplasty
<25 patients/arm
Becker, et al.
1996
Rapid imaging of infections with a monoclonal antibody fragment (LeukoScan)
<25 patients
Bernard, et al.
2004
Value of preoperative investigations in diagnosing prosthetic joint infection: retrospective
cohort study and literature review
Not best available
evidence
Boubaker, et al.
1995
Immunoscintigraphy with antigranulocyte monoclonal antibodies for the diagnosis of
septic loosening of hip prostheses
Not best available
evidence
Britton, et al.
1997
Clinical evaluation of technetium-99m infecton for the localisation of bacterial infection
Not relevant - not
specific to pji
Chacko, et al.
2003
Applications of fluorodeoxyglucose positron emission tomography in the diagnosis of
infection
Not best available
evidence
Chacko, et al.
2002
The importance of the location of fluorodeoxyglucose uptake in periprosthetic infection in
painful hip prostheses
Not best available
evidence
Chafetz, et al.
1985
Multinuclide digital subtraction imaging in symptomatic prosthetic joints
Not best available
evidence
Chik, et al.
1996
Tc-99m stannous colloid-labeled leukocyte scintigraphy in the evaluation of the painful
arthroplasty
Not best available
evidence
114
v0.1 03.25.10
Author
Title
Crokaert, et al.
1982
Gallium-67 citrate as an aid to the diagnosis of infection in hip surgery
<25 patients/arm
Dams, et al.
2000
99mTc-PEG liposomes for the scintigraphic detection of infection and inflammation:
clinical evaluation
<25 patients
Datz, et al.
1994
The efficacy of indium-111-polyclonal IgG for the detection of infection and inflammation
Not relevant - not
specific to pji
Datz, et al.
1986
Not relevant - not
specific to pji
de Lima Ramos, et al.
1996
de Winter, et al.
2001
Simultaneous administration of 99Tcm-HMPAO-labelled autologous leukocytes and
111In-labelled non-specific polyclonal human immunoglobulin G in bone and joint
infections
Fluorine-18 fluorodeoxyglucose-position emission tomography: a highly accurate imaging
modality for the diagnosis of chronic musculoskeletal infections
<25 patients
<25 patients
Demirkol, et al.
1997
99Tc(m)-polyclonal IgG scintigraphy in the detection of infected hip and knee prostheses
Not best available
evidence
Devillers, et al.
1995
Technetium-99m hexamethylpropylene amine oxime leucocyte scintigraphy for the
diagnosis of bone and joint infections: a retrospective study in 116 patients
Not best available
evidence
El Esper, et al.
2004
The usefulness of 99mTc sulfur colloid bone marrow scintigraphy combined with 111In
leucocyte scintigraphy in prosthetic joint infection
Not best available
evidence
Feith, et al.
1976
Strontium 87mSr bone scanning for the evaluation of total hip replacement
Not relevant - not
specific to pji
Flivik, et al.
1993
Technetium-99m-nanocolloid scintigraphy in orthopedic infections: a comparison with
indium-111-labeled leukocytes
<25 patients
Gomez-Luzuriaga, et
al. 1988
Scintigraphy with Tc, Ga and In in painful total hip prostheses
<25 patients/arm
115
v0.1 03.25.10
Author
Title
Hall, et al.
1998
Evaluation of the efficacy of 99mTc-Infecton, a novel agent for detecting sites of infection
Not relevant - not
specific to pji
Henderson, et al.
1996
The value of skeletal scintigraphy in predicting the need for revision surgery in total knee
replacement
Not best available
evidence
Itasaka, et al.
2001
Not best available
evidence
Ivancevic, et al.
2002
Imaging of low-grade bone infection with a technetium-99m labelled monoclonal antiNCA-90 Fab' fragment in patients with previous joint surgery
<25 patients
Iyengar, et al.
2005
Role of 99mTc Sulesomab in the diagnosis of prosthetic joint infections
Not best available
evidence
Jaruskova, et al.
2006
Role of FDG-PET and PET/CT in the diagnosis of prolonged febrile states
Not relevant - not
specific to pji
Jensen, et al.
1990
Tc-99m-MDP scintigraphy not informative in painful total hip arthroplasty
Not relevant - not
specific to pji
Larikka, et al.
2001
Improved method for detecting knee replacement infections based on extended combined
99mTc-white blood cell/bone imaging
Not best available
evidence
Larikka, et al.
2001
Extended combined 99mTc-white blood cell and bone imaging improves the diagnostic
accuracy in the detection of hip replacement infections
Not best available
evidence
Larikka, et al.
2002
Comparison of 99mTc ciprofloxacin, 99mTc white blood cell and three-phase bone
imaging in the diagnosis of hip prosthesis infections: improved diagnostic accuracy with
extended imaging time
Not best available
evidence
Li, et al.
1994
Bone scintigraphy of hip prostheses: Can analysis of patterns of abnormality improve
accuracy?
Not relevant - not
specific to pji
Lieberman, et al.
1993
Evaluation of painful hip arthroplasties. Are technetium bone scans necessary?
Not best available
evidence
116
v0.1 03.25.10
Author
Title
Love, et al.
2001
Role of nuclear medicine in diagnosis of the infected joint replacement
Narrative review,
Manthey, et al.
2002
The use of [18 F]fluorodeoxyglucose positron emission tomography to differentiate
between synovitis, loosening and infection of hip and knee prostheses
<25 patients
McInerney, et al.
1978
Technetium 99Tcm pyrophosphate scanning in the assessment of the painful hip prosthesis
Insufficient Data
Merkel, et al.
1985
Comparison of indium-labeled-leukocyte imaging with sequential technetium-gallium
scanning in the diagnosis of low-grade musculoskeletal sepsis. A prospective study
<25 patients
Merkel, et al.
1986
Sequential technetium-99m HMDP-gallium-67 citrate imaging for the evaluation of
infection in the painful prosthesis
>10% prostheses
already removed
Miles, et al.
1992
Scintigraphic abnormalities in patients with painful hip replacements treated
conservatively
Insufficient Data
Moragas, et al.
1991
99Tcm-HMPAO leucocyte scintigraphy in the diagnosis of bone infection
Not best available
evidence
Mountford, et al.
1986
99Tcm-MDP, 67Ga-citrate and 111In-leucocytes for detecting prosthetic hip infection
Not best available
evidence
Mumme, et al.
2005
Diagnostic values of positron emission tomography versus triple-phase bone scan in hip
arthroplasty loosening
Insufficient Data
Nijhof, et al.
1997
Hip and knee arthroplasty infection. In-111-IgG scintigraphy in 102 cases
Not best available
evidence
Nijhof, et al.
1997
Evaluation of infections of the locomotor system with indium-111-labeled human IgG
scintigraphy
Not best available
evidence
Ouzounian, et al.
1987
Evaluation of musculoskeletal sepsis with indium-111 white blood cell imaging
<25 patients
117
v0.1 03.25.10
Author
Oyen, et al.
1990
Title
Detection of subacute infectious foci with indium-111-labeled autologous leukocytes and
indium-111-labeled human nonspecific immunoglobulin G: a prospective comparative
study
Scintigraphic detection of bone and joint infections with indium-111-labeled nonspecific
polyclonal human immunoglobulin G
Oyen, et al.
1992
Diagnosis of bone, joint, and joint prosthesis infections with In-111-labeled nonspecific
human immunoglobulin G scintigraphy
Not best available
evidence
Pakos, et al.
2007
Prosthesis infection: diagnosis after total joint arthroplasty with antigranulocyte
scintigraphy with 99mTc-labeled monoclonal antibodies--a meta-analysis
Systematic review,
Pakos, et al.
2007
Use of (99m)Tc-sulesomab for the diagnosis of prosthesis infection after total joint
arthroplasty
<25 patients
Palermo, et al.
1998
Comparison of technetium-99m-MDP, technetium-99m-WBC and technetium-99m-HIG
in musculoskeletal inflammation
Not relevant - not
specific to pji
Palestro, et al.
1990
Total-hip arthroplasty: periprosthetic indium-111-labeled leukocyte activity and
complementary technetium-99m-sulfur colloid imaging in suspected infection
Not best available
evidence
Palestro, et al.
1992
Diagnosis of musculoskeletal infection using combined In-111 labeled leukocyte and Tc99m SC marrow imaging
Not relevant - not
specific to pji
Palestro, et al.
1991
Infected knee prosthesis: diagnosis with In-111 leukocyte, Tc-99m sulfur colloid, and Tc99m MDP imaging
Not best available
evidence
Parvizi, et al.
2006
Periprosthetic infection: What are the diagnostic challenges?
Not best available
evidence
Pearlman, et al.
1980
The painful hip prosthesis: value of nuclear imaging in the diagnosis of late complications
Insufficient Data
Pelosi, et al.
2004
99mTc-HMPAO-leukocyte scintigraphy in patients with symptomatic total hip or knee
arthroplasty: improved diagnostic accuracy by means of semiquantitative evaluation
Not best available
evidence
Oyen, et al.
1991
Not relevant - not
specific to pji
Not relevant - not
specific to pji
118
v0.1 03.25.10
Author
Title
Pill, et al.
2006
Comparison of fluorodeoxyglucose positron emission tomography and (111)indium-white
blood cell imaging in the diagnosis of periprosthetic infection of the hip
Not best available
evidence
Prchal, et al.
1987
Detection of musculoskeletal infection with the indium-III leukocyte scan
Not relevant - not
specific to pji
Pring, et al.
1986
Indium-granulocyte scanning in the painful prosthetic joint
Duplicate data
Reinartz, et al.
2009
FDG-PET in patients with painful hip and knee arthroplasty: technical breakthrough or just
more or the same
Systematic review,
Reinartz, et al.
2005
Radionuclide imaging of the painful hip arthroplasty: positron-emission tomography
versus triple-phase bone scanning
Not best available
evidence
Reuland, et al.
1991
Detection of infection in postoperative orthopedic patients with technetium-99m-labeled
monoclonal antibodies against granulocytes
Not relevant - not
specific to pji
Rosas, et al.
1998
<25 patients per group
Rubello, et al.
1995
Three-phase bone scintigraphy pattern of loosening in uncemented hip prostheses
Not relevant - not
specific to pji
Rubello, et al.
2004
Role of anti-granulocyte Fab' fragment antibody scintigraphy (LeukoScan) in evaluating
bone infection: acquisition protocol, interpretation criteria and clinical results
Not relevant - not
specific to pji
Rubello, et al.
2008
Diagnosis of infected total knee arthroplasty with anti-granulocyte scintigraphy: the
importance of a dual-time acquisition protocol
Not best available
evidence
Rubin, et al.
1989
111In-labeled nonspecific immunoglobulin scanning in the detection of focal infection
Not relevant - not
specific to pji
Rushton, et al.
1982
The value of technetium and gallium scanning in assessing pain after total hip replacement
Not best available
evidence
119
v0.1 03.25.10
Author
Title
Ryan,
2002
Leukoscan for orthopaedic imaging in clinical practice
Not best available
evidence
Sayle, et al.
1985
Indium-111 chloride imaging in the detection of infected prostheses
<25 patients
Sciuk, et al.
1992
White blood cell scintigraphy with monoclonal antibodies in the study of the infected
endoprosthesis
Not best available
evidence
Serafini, et al.
1991
Clinical evaluation of a scintigraphic method for diagnosing inflammations/infections
using indium-111-labeled nonspecific IgG
Not relevant - not
specific to pji
Sfakianakis, et al.
1982
Comparisons of scintigraphy with In-111 leukocytes and Ga-67 in the diagnosis of occult
sepsis
Not relevant - not
specific to pji
Simonsen, et al.
2007
White blood cell scintigraphy for differentiation of infection and aseptic loosening: a
retrospective study of 76 painful hip prostheses
Not best available
evidence
Smith, et al.
2001
Radionuclide bone scintigraphy in the detection of significant complications after total
knee joint replacement
Not best available
evidence
Spinelli,
1976
The role of scintigraphy in the diagnosis of late complications of total prosthesis of the hip.
(Infection, loosening, ossification)
Insufficient Data
Streule, et al.
1988
99Tcm-labelled HSA-nanocolloid versus 111In oxine-labelled granulocytes in detecting
skeletal septic process
<25 eligible patients
Stumpe, et al.
2004
FDG PET for differentiation of infection and aseptic loosening in total hip replacements:
comparison with conventional radiography and three-phase bone scintigraphy
Not best available
evidence
Stumpe, et al.
2006
The value of FDG-PET in patients with painful total knee arthroplasty
Not best available
evidence
Taylor, et al.
1989
A simple method of identifying loosening or infection of hip prostheses in nuclear
medicine
Not best available
evidence
Tehranzadeh, et al.
1981
Radiological evaluation of painful total hip replacement
Not best available
evidence
120
v0.1 03.25.10
Author
Title
Van Acker, et al.
2001
FDG-PET, 99mtc-HMPAO white blood cell SPET and bone scintigraphy in the evaluation
of painful total knee arthroplasties
<25 patients
Vanquickenborne, et
al. 2003
The value of (18)FDG-PET for the detection of infected hip prosthesis
<25 patients per arm
Vicente, et al.
2004
Diagnosis of orthopedic infection in clinical practice using Tc-99m sulesomab
(antigranulocyte monoclonal antibody fragment Fab'2)
Not best available
evidence
Vinjamuri, et al.
1996
Comparison of 99mTc infecton imaging with radiolabelled white-cell imaging in the
evaluation of bacterial infection
Not relevant - not
specific to pji
Virolainen, et al.
2002
Not best available
evidence
von Rothenburg, et al.
2004
Imaging of infected total arthroplasty with Tc-99m-labeled antigranulocyte antibody
Fab'fragments
Not best available
evidence
Weiss, et al.
1979
99mTc-methylene diphosphonate bone imaging in the evaluation of total hip prostheses
<25 patients/arm
Wellman, et al.
1988
Evaluation of metallic osseous implants with nuclear medicine
Insufficient Data
Williams, et al.
1977
99Tcm-diphosphonate scanning as an aid to diagnosis of infection in total hip joint
replacements
<25 patients/arm
Williams, et al.
1981
Gallium-67 scanning in the painful total hip replacement
Not best available
evidence
Wolf, et al.
2003
Localization and diagnosis of septic endoprosthesis infection by using 99mTc-HMPAO
labelled leucocytes
Not best available
evidence
Wukich, et al.
1987
Diagnosis of infection by preoperative scintigraphy with indium-labeled white blood cells
<25 patients with
prosthesis
121
v0.1 03.25.10
Author
Title
Yapar, et al.
2001
The efficacy of technetium-99m ciprofloxacin (Infecton) imaging in suspected orthopaedic
infection: a comparison with sequential bone/gallium imaging
<25 patients
Zhuang, et al.
2002
Persistent non-specific FDG uptake on PET imaging following hip arthroplasty
<25 patients
Zhuang, et al.
2001
The promising role of 18F-FDG PET in detecting infected lower limb prosthesis implants
Not best available
evidence
Zoccali, et al.
2009
The role of FDG-PET in distinguishing between septic and aseptic loosening in hip
prosthesis: a review of literature
Systematic review,
122
v0.1 03.25.10
N
Index Test
avoided
described
result(s) reported
Author
Level of
Evidence
STUDY QUALITY
Table 50. Nuclear Imaging - Quality
Nagoya
46
3-phase bone scintigraphy
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
Klett
28
antigranulocyte antibody BW 250/183
scintigraphy
I
?
●
●
●
●
●
●
●
●
●
●
●
●
●
In-111 leukocyte scan
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
● = Yes
○ = No
? = Unclear
Glithero 25
Joseph
36
Joseph
58
Joseph
36
Joseph
58
Glithero 31
Glithero 45
In-111 leukocyte/Tc-99m sulfur colloid
scans
In -111 leukocyte/Tc-99m sulfur
colloid scans
colloid scans and with blood pooling
and flow phase data
colloid scans and with blood pooling
and flow phase data
Tc-99m HMPAO leukocyte
scintigraphy
Tc-99m HMPAO or In-111-oxine
leukocyte scan
123
v0.1 03.25.10
Index Test
avoided
described
result(s) reported
N
Level of
Evidence
Author
Table 50. Nuclear Imaging – Quality (Continued)
Glithero
56
Tc-99m HMPAO or In-111-oxine
leukocyte scan
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
Teller
166
Tc-99m HPD/In-111 leukocyte scan
I
?
●
●
●
●
●
●
●
●
●
?
●
●
●
Reing
79
Ga-67 scan
II
?
○
●
●
●
●
●
●
○
●
●
●
●
●
Pring
40
In-111 granulocyte scan
II
?
○
●
●
●
●
●
●
●
●
?
●
●
●
Mulamba
30
In-111 leukocyte/sulfur colloid scan
II
?
○
●
●
●
●
●
●
○
●
●
●
●
●
Rand
38
II
●
○
●
●
●
●
●
●
●
●
?
●
●
●
Magnuson
98
II
?
○
●
●
●
●
●
●
?
●
?
●
●
●
Johnson
29
II
●
●
●
●
●
●
●
●
○
●
●
●
●
●
Kraemer
33
sequential scan and aspiration
II
?
?
●
●
●
●
●
?
○
●
●
●
●
●
Kraemer
43
sequential Tc-99m bone scan/Ga-67
scan
II
?
?
●
●
●
●
●
?
○
●
●
●
●
●
Johnson
29
Tc-99m HDP/In-111 leukocyte scan
II
●
●
●
●
●
●
●
●
○
●
●
●
●
●
● = Yes
○ = No
? = Unclear
124
v0.1 03.25.10
avoided
described
result(s) reported
II
?
○
●
●
●
●
●
●
●
●
?
●
●
●
II
?
○
●
●
●
●
●
●
●
●
?
●
●
●
Tc-99m –HMPAO scan
II
●
●
●
●
●
●
●
○
●
●
●
●
●
○
26
II
●
●
●
●
●
●
●
○
●
?
?
●
●
○
Savarino
26
II
●
●
●
●
●
●
●
○
●
?
?
●
●
○
Benitez
Segura
77
II
●
●
●
●
●
●
●
●
○
●
●
●
●
●
Benitez
Segura
77
II
●
●
●
●
●
●
●
●
○
●
●
●
●
●
Benitez
Segura
77
II
●
●
●
●
●
●
●
●
○
●
●
●
●
●
Benitez
Segura
77
II
●
●
●
●
●
●
●
●
○
●
●
●
●
●
● = Yes
○ = No
? = Unclear
Author
N
Scher
91
Scher
40
Savarino
26
Savarino
Index Test
Tc-99m HDP/indium-111-labeled
leukocyte scan (positive if
incongruent scans)
Tc-99m HDP/indium-111-labeled
leukocyte scan (positive if
incongruent scans)
Tc-99m HMPAO leukocyte
scintigraphy
Tc-99m HMPAO leukocyte/Tc-99m
stannous microcolloid bone marrow
scan
Tc-99m HMPAO leukocyte/Tc-99m
stannous microcolloid bone marrow
scan/Tc-99m MDP bone scan
Tc-99m MDP bone scan
Level of
Evidence
125
v0.1 03.25.10
Index Test
avoided
described
result(s) reported
N
Level of
Evidence
Author
Bernay
31
Tc-99m MDP scintigraphy
II
●
●
?
●
●
●
●
○
●
●
?
●
●
●
Levitsky
58
Tc-99m MDP TPBI
II
●
?
●
●
●
●
●
●
●
●
●
?
●
○
Levitsky
54
II
●
?
●
●
●
●
●
?
●
●
●
?
●
○
Pons
78
II
●
○
●
●
●
●
●
●
○
●
?
?
●
●
Bernay
31
Tc-99m nanocolloid scintigraphy
II
●
●
?
●
●
●
●
○
●
●
?
●
●
●
Sudanese
35
Tc-99m-labelled granulocyte bone
scan
II
?
?
●
●
●
●
●
●
○
●
●
●
●
●
Love
59
WBC/marrow imaging
II
?
●
●
●
●
●
●
●
○
●
?
●
●
●
Chryssikos
127
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
Delank
27
II
●
●
?
●
●
●
●
●
○
●
?
●
●
●
● = Yes
○ = No
? = Unclear
Tc-99m MDP TPBI and plain
radiographs
Tc-99m MDP, Tc-99 HmPAO white
blood cells scintigraphy (positive if
areas of increased isotope uptake for
Tc were congruent with high levels
of white blood cell labelled with Tc)
FDG-PET - increased FDG uptake at
prosthesis-bone interface
FDG-PET - FDG uptake in the
periprosthetic soft tissue
126
v0.1 03.25.10
avoided
described
result(s) reported
II
?
●
●
●
●
●
●
●
○
●
?
●
●
●
II
?
●
●
●
●
●
●
●
○
●
?
●
●
●
II
?
●
●
●
●
●
●
●
○
●
?
●
●
●
II
?
●
●
●
●
●
●
●
○
●
?
●
●
●
● = Yes
○ = No
? = Unclear
Author
N
Love
59
Love
59
Love
59
Love
59
Index Test
FDG-PET - activity at boneprosthesis interface (of femoral
component for hip, femoral or tibial
for knee)
FDG-PET - any periprosthetic
activity
FDG-PET - semiquantitative
analysis of bone-prostesis interface
activity (target-background ratio)
FDG-PET/WBC marrow - any
perisprosthetic activity on FDG
image without corresponding
activity on marrow image
Level of
Evidence
127
v0.1 03.25.10
STUDY RESULTS
Figure 13. Technetium-labeled-Leukocyte Imaging Results – Likelihood Ratios
StudyId
StudyId
Benitez Segura
Benitez Segura
Glithero - Hip and Knee - Tc or In
Glithero - Hip and Knee - Tc or In
Glithero - Hip and Knee - Tc only
Glithero - Hip and Knee - Tc only
Sudanese
Sudanese
Savarino
Savarino
Glithero - Hip - Tc or In
Glithero - Hip - Tc or In
1 2 5 10
.1 .2
DLR POSITIVE
.5
1
DLR NEGATIVE
128
v0.1 03.25.10
Figure 14. Indium-labeled-Leukocyte Imaging Results - Likelihood Ratios
StudyId
StudyId
Pring
Pring
Johnson
Johnson
Magnuson
Magnuson
Rand
Rand
Glithero
Glithero
1
2
5
10
.1
.2
DLR POSITIVE
.5
1
DLR NEGATIVE
Figure 15. Combined Leukocyte/Bone Imaging Results – Likelihood Ratios
StudyId
StudyId
Pons
Pons
Scher
Scher
Johnson
Johnson
Teller
Teller
COMBINED
COMBINED
1
2
5
10
0 .1 .2
.5
1
DLR NEGATIVE
DLR POSITIVE
129
v0.1 03.25.10
Figure 16. Combined Leukocyte/Bone Marrow Imaging Results - Likelihood Ratios
StudyId
StudyId
Joseph - Hip
Joseph - Hip
Joseph - Hip with phase data
Joseph - Hip with phase data
Joseph - Hip & Knee
Joseph - Hip & Knee
Joseph - Hip & Knee with phase data
Joseph - Hip & Knee with phase data
Mulamba
Mulamba
Benitez Segura
Benitez Segura
Love
Love
1 2
5 10
.1 .2
DLR POSITIVE
.5
1
DLR NEGATIVE
Figure 17. FDG-PET Imaging Results - Likelihood Ratios
StudyId
StudyId
Chryssikos - increased uptake at BPI
Chryssikos - increased uptake at BPI
Delank - uptake in the periprosthetic soft tissue
Delank - uptake in the periprosthetic soft tissue
Love - activity at BPI
Love - activity at BPI
Love - any periprosthetic activity
Love - any periprosthetic activity
Love - semiquantitative analysis of BPI activity
Love - semiquantitative analysis of BPI activity
Love - FDG-PET/WBC marrow
Love - FDG-PET/WBC marrow
1 2 5 10
.1 .2
.5
1
DLR NEGATIVE
DLR POSITIVE
130
v0.1 03.25.10
Figure 18. Technetium-99m Bone Imaging Results - Likelihood Ratios
StudyId
StudyId
Levitsky
Levitsky
Benitez Segura
Benitez Segura
Bernay
Bernay
Nagoya
Nagoya
1
2
5
10
.1.2
.5
1
DLR NEGATIVE
DLR POSITIVE
*Benitez Segura used 2-phase rather than 3-phase bone imaging
131
v0.1 03.25.10
Figure 19. Other Nuclear Imaging Results - Likelihood Ratios
StudyId
StudyId
Reing - Ga-67 scan
Reing - Ga-67 scan
Kraemer - Sequential bone/Ga-67 scan
Kraemer - Sequential bone/Ga-67 scan
Kraemer - Sequential scan or aspiration
Kraemer - Sequential scan or aspiration
Klett - antibody BW 250/183 scintigraphy
Klett - antibody BW 250/183 scintigraphy
Bernay - nanocolloid scintigraphy
Bernay - nanocolloid scintigraphy
1 2 5 10
.1 .2
.5
1
DLR NEGATIVE
DLR POSITIVE
132
v0.1 03.25.10
Table 51. Technetium-99m-labeled-Leukocyte Imaging
Level of
Evidence
Author
N
I
Glithero
45
II
Savarino
26
II
Savarino
26
II
Savarino
26
II
Sudanese
35
Test
Tc-99m
HMPAO or
In-111oxine
leukocyte
scan
Tc-99mHMPAO
granulocyte
scintigraphy
Tc-99mHMPAO
granulocyte
scintigraphy
Tc-99mHMPAO
granulocyte
scintigraphy
Tc-99m
granulocyte
bone scan
Negative
Positive
Likelihood Likelihood Sensitivity Specificity
(95% CI) (95% CI)
Ratio
Ratio
(95% CI)
(95% CI)
Reference
Standard
Joint
Intraoperative
cultures
Hip
16.5
(0.91,
298.82)
0.76
(0.56,
1.03)
0.23
(0.05,
0.54)
Intraoperative
cultures
Hip
7.12
(0.44,
116.34)
0.71
(0.5, 1.01)
Histology
Hip
12.69
(0.77,
208.34)
Intraoperative
cultures and
histology
Hip
Intraoperative
cultures
Hip
TP
FP
FN
TN
1
(0.89, 1)
3
0
10
32
0.31
(0.11,
0.59)
1
(0.69, 1)
5
0
11
10
0.6
(0.37,
0.96)
0.42
(0.15,
0.72)
1
(0.77, 1)
5
0
7
14
17
(1.04,
277.87)
0.52
(0.28,
0.94)
0.5
(0.19,
0.81)
1
(0.79, 1)
5
0
5
16
7.56
(2.8,
20.39)
0.06
(0, 0.94)
1
(0.63, 1)
0.89
(0.71,
0.98)
8
3
0
24
133
v0.1 03.25.10
Table 51. Technetium-99m-labeled-Leukocyte Imaging (Continued)
Level of
Evidence
I
I
II
Author
Glithero
Glithero
Benitez
Segura
Reference
Standard
Joint
Negative
Positive
(95% CI) (95% CI)
Ratio
Ratio
(95% CI)
(95% CI)
TP
FP
FN
TN
1
(0.84, 1)
5
0
5
21
0.44
(0.22,
0.69)
1
(0.91, 1)
8
0
10
38
0.96
(0.82, 1)
0.31
(0.18,
0.45)
27
34
1
15
N
Test
31
Tc-99m
HMPAO
leukocyte
scintigraphy
Mixed
(20
Intraoperative
hip,
cultures
11
knee)
22
(1.33,
362.92)
0.51
(0.28,
0.93)
0.5
(0.19,
0.81)
56
Tc-99m
HMPAO or
In-111oxine
leukocyte
scan
Mixed
(45
Intraoperative
hip,
cultures
11
knee)
34.89
(2.12,
573.23)
0.56
(0.37,
0.84)
77
Tc-99m
HMPAO
leukocyte
scintigraphy
Mixed
(48
Intraoperative
hip,
cultures
29
knee)
1.39
(1.14, 1.7)
0.12
(0.02,
0.84)
134
v0.1 03.25.10
Table 52. Indium-111-labeled-Leukocyte Imaging
Level of
Evidence
I
II
II
II
II
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
0.63
(0.37, 1.06)
0.38
(0.09,
0.76)
1
(0.8, 1)
3
0
5
17
N
Test
Reference
Standard
25
In-111
leukocyte
scan
Intraoperative
cultures
Hip
14
(0.81,
242.78)
38
In-111
leukocyte
scan
at least 2 of:
1)positive
culture results
2)acute
inflammatory
histologic
findings
3)clinical
sepsis with pus
within the joint
Knee
5.56
(1.92,
16.09)
0.2
(0.07, 0.56)
0.83
(0.59,
0.96)
0.85
(0.62,
0.97)
15
3
3
17
Magnuson 98
In-111
leukocyte
scan
Intraoperative
cultures or
histology
Mixed
3.25
(2.02, 5.23)
0.16
(0.08, 0.36)
0.88
(0.76,
0.95)
0.73
(0.58,
0.85)
44
13
6
35
29
In-111
leukocyte
scan
Intraoperative
cultures
Mixed
1.9
(1.21, 2.98)
0.1
(0.01, 1.54)
1
(0.66, 1)
0.5
(0.27,
0.73)
9
10
0
10
40
In-111
granulocyte
scan
Intraoperative
cultures or
histology or
deep abscess
Mixed
8.96
(2.77,
28.94)
0.03
(0, 0.46)
1
(0.81, 1)
0.91
(0.71,
0.99)
18
2
0
20
Author
Glithero
Rand
Johnson
Pring
TP FP FN TN
135
v0.1 03.25.10
Table 53. Combined Leukocyte/Bone Imaging
Level of
Evidence
II
II
Author
Pons
Scher
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
N
Test
Reference
Standard
78
Tc-99m
MDP, Tc-99
HMPAO
leukocyte
scintigraphy
Intraoperative
cultures and
histology
Hip
6.3
(2.65,
14.98)
0.44
(0.24, 0.83)
0.6
(0.32,
0.84)
0.9
(0.8, 0.96)
9
6
6
57
Tc-99m
HDP/In-111
leukocyte
scan
At least 2 of:
1)positive
intraoperative
cultures (either
broth or plate)
2)intraoperative
findings of gross
purulence within
the joint 3)final
permanent
histologic section
incidcating acute
inflammation
based on ≥10
PMN/HPF in 5
areas
Hip
8.1
(3.22,
20.35)
0.43
(0.2, 0.93)
0.6
(0.26,
0.88)
0.93
(0.85,
0.97)
6
6
4
75
91*
TP FP FN TN
136
v0.1 03.25.10
Table 53. Combined Leukocyte/Bone Imaging (Continued)
Level of
Evidence
II
Author
Scher
Test
Reference
Standard
Tc-99m
HDP/In111
leukocyte
scan
At least 2 of:
1)positive
intraoperative
cultures (either
broth or plate)
2)intraoperative
findings of gross
purulence within
the joint 3)final
permanent
histologic section
incidcating acute
inflammation
based on ≥10
PMN/HPF in 5
areas
N
40*
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
Knee
4.06
(1.83, 8.98)
0.15
(0.04, 0.56)
0.88
(0.64,
0.99)
Tc-99m
Intraoperative
HPD/In2.86
0.47
I
Teller 166
cultures of frank Mixed
111
(1.85, 4.44) (0.27, 0.82)
leukocyte
purulence
scan
Tc-99m
HDP/In17.78
Intraoperative
0.12
II
Johnson 29
Mixed
111
(2.6,
cultures
(0.02, 0.74)
leukocyte
121.78)
scan
*Three hip scans and one knee scan regarded as equivocal were excluded from the analysis
TP FP FN
TN
0.78
(0.56,
0.93)
15
5
2
18
0.64
(0.41,
0.83)
0.78
(0.7, 0.84)
14
32
8
112
0.89
(0.52, 1)
0.95
(0.75, 1)
8
1
1
19
137
v0.1 03.25.10
Table 54. Combined Leukocyte/Bone Marrow Imaging
Level of
Evidence
I
I
Author
Joseph
Joseph
N
Test
36
In-111
leukocyte/Tc99m sulfur
colloid scans
36
In-111
colloid scans
and with
blood pooling
and flow
phase data
Reference
Standard
at least 2 of:
1)positive
intraoperative
culture 2)final
histology (>10
PMN/HPF in 5
areas)
3)intraoperative
findings of gross
purulence within
the joint
at least 2 of:
1)positive
intraoperative
culture 2)final
histology (>10
PMN/HPF in 5
areas)
3)intraoperative
findings of gross
purulence within
the joint
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
Hip
19.6
(1.11,
347.03)
0.66
(0.42, 1.05)
0.33
(0.07, 0.7)
1
(0.87, 1)
3
0
6
27
Hip
30.8
(1.87,
508.31)
0.46
(0.23, 0.91)
0.56
(0.21,
0.86)
1
(0.87, 1)
5
0
4
27
TP FP FN TN
138
v0.1 03.25.10
Table 54. Combined Leukoycte/Bone Marrow Imaging (Continued)
Level of
Evidence
I
I
II
Author
N
Test
In-111
colloid scans
Joseph
58
Joseph
In-111
colloid scans
58
and with
blood pooling
and flow
phase data
Mulamba 30
In-111
colloid scans
Reference
Standard
at least 2 of:
1)positive
intraoperative
culture 2)final
histology (>10
PMN/HPF in 5
areas)
3)intraoperative
findings of
gross purulence
within the joint
at least 2 of:
1)positive
intraoperative
culture 2)final
histology (>10
PMN/HPF in 5
areas)
3)intraoperative
findings of
gross purulence
within the joint
Intraoperative
cultures
Joint
Positive
Negative
TP FP FN TN
Ratio
Ratio
(95% CI) (95% CI)
(95% CI)
(95% CI)
Mixed
(36
hip,
22
knee)
41.25
(2.5,
681.7)
0.54
(0.34,
0.85)
0.47
(0.21,
0.73)
1
(0.92, 1)
7
0
8
43
Mixed
(36
hip,
22
knee)
28.67
(4, 205.52)
0.34
(0.17, 0.7)
0.67
(0.38,
0.88)
0.98
(0.88, 1)
10
1
5
42
Hip
32.14
(2.08,
497.33)
0.11
(0.02, 0.5)
0.92
(0.64, 1)
1
(0.8, 1)
12
0
1
17
139
v0.1 03.25.10
Table 54. Combined Leukoycte/Bone Marrow Imaging (Continued)
Level of
Evidence
II
II
II
Author
Benitez
Segura
Benitez
Segura
Love
N
77
77
59
Test
Tc-99m
HMPAO
leukocyte/Tc99m stannous
microcolloid
bone marrow
scan
Tc-99m
HMPAO
leukocyte/Tc99m stannous
microcolloid
bone marrow
scan/Tc-99m
MDP bone
scan
In-111
colloid scans
Positive
Negative
TP FP FN TN
Ratio
Ratio
(95% CI) (95% CI)
(95% CI)
(95% CI)
Reference
Standard
Joint
Intraoperative
cultures
Mixed
(48
hip,
29
knee)
45.5
(6.52,
317.44)
0.07
(0.02,
0.28)
0.93
(0.76,
0.99)
0.98
(0.89, 1)
26
1
2
48
Intraoperative
cultures
Mixed
(48
hip,
29
knee)
45.5
(6.52,
317.44)
0.07
(0.02,
0.28)
0.93
(0.76,
0.99)
0.98
(0.89, 1)
26
1
2
48
Intraoperative
cultures or
histology
Mixed
(40
hip,
19
knee)
9.81
(3.62,
26.54)
0.02
(0, 0.33)
1
(0.86, 1)
0.91
(0.76,
0.98)
25
3
0
31
140
v0.1 03.25.10
Table 55. Gallium-67 Imaging
Level of
Evidence
II
Author
Reing
N
Test
Reference
Standard
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
111
(7.0, 1765)
0.07
(0.02, 0.34)
0.95
(0.75, 1)
(95% CI) (95% CI)
TP
FP
FN
TN
1
(0.94, 1)
19
0
1
59
79
Ga-67
scan
Intraoperative
cultures
Mixed
(67
hips,
12
knee, 1
elbow)
Intraoperative
cultures
Hip
24.36
(1.44, 410)
0.62
(0.4, 0.94)
0.38
(0.14,
0.68)
1
(0.88, 1)
5
0
8
30
Intraoperative
cultures
Hip
14
(1.96, 100)
0.38
(0.17, 0.84)
0.64
(0.31,
0.89)
0.95
(0.77, 1)
7
1
4
21
II
Kraemer
43
Sequential
Tc-99m
bone
scan/Ga67 scan
II
Kraemer
33
Sequential
scan or
aspiration
141
v0.1 03.25.10
Table 56. FDG-PET Imaging
Level of
Evidence
I
II
Author
N
Chryssikos 127
Delank
27
Test
FDG-PET increased
FDG uptake
at prosthesisbone
interface
FDG-PET FDG uptake
in the
periprosthetic
soft tissue
Reference
Standard
At least 1 of: 1)an
open wound or
sinus
communicating
with the joint 2)
systemic infection
with pain in the hip
and purulent fluid
within the joint
3)positive result on
at least 3 tests
(ESR, CRP, joint
aspiration,
intraoperative
frozen section, and
intraoperative
culture)
Intraoperative
Macroscopic,
Microbiological,
and
Histopathological
examinations
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
Hip
11.39
(5.51,
23.58)
0.16
(0.07, 0.37)
0.85
(0.68,
0.95)
0.93
(0.85,
0.97)
28
7
5
87
Mixed
(22
hip, 5
knee)
19.17
(1.05, 348)
0.6
(0.3, 1.18)
0.4
(0.05,
0.85)
1
(0.85, 1)
2
0
3
22
TP FP FN TN
142
v0.1 03.25.10
Table 56. FDG-PET Imaging (Continued)
Level of
Evidence
Author
N
Test
Reference
Standard
Intraoperative
cultures or
histology
Intraoperative
cultures or
histology
II
Love
59
FDG-PET - activity
at bone-prosthesis
interface
II
Love
59
FDG-PET - any
periprosthetic
activity
II
II
Love
Love
59
59
FDG-PET semiquantitative
analysis of boneprosthesis interface
activity (targetbackground ratio)
FDG-PET/WBC
marrow - any
perisprosthetic
activity on FDG
image without
corresponding
activity on marrow
image
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio (95%
CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
0.93
(0.58, 1.5)
1.09
(0.62, 1.9)
0.52
(0.31,
0.72)
0.44
(0.27,
0.62)
13
19
12
15
1.09
(0.96, 1.23)
0.19
(0.01, 3.56)
1
(0.86, 1)
0.09
(0.02,
0.24)
25
31
0
3
Joint
Mixed
(40
hip, 19
knee)
Mixed
(40
hip, 19
knee)
TP FP FN TN
Intraoperative
cultures or
histology
Mixed
(40
hip, 19
knee)
12.24
(1.66, 90.5)
0.66
(0.49, 0.89)
0.36
(0.18,
0.57)
0.97
(0.85, 1)
9
1
16
33
Intraoperative
cultures or
histology
Mixed
(40
hip, 19
knee)
1.48
(1.14, 1.93)
0.11
(0.02, 0.82)
0.96
(0.8, 1)
0.35
(0.2, 0.54)
24
22
1
12
143
v0.1 03.25.10
Table 57. Technetium-99m Bone Imaging
Level of
Evidence
I
II
II
Author
Nagoya
Bernay
Benitez
Segura
N
Test
46
Tc-99m 3phase bone
scintigraphy
31
Tc-99m
MDP 3phase
scintigraphy
77
Tc-99m
MDP 2phase bone
scintigraphy
Reference
Standard
at least 1 of:
1)intraoperative
or open biopsy
tissue culture,
2)histology,
3)visibly
purulent
synovial fluid
Pathological
and gross
operative
findings
Intraoperative
cultures
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
Hip
8.53
(2.88,
25.25)
0.13
(0.04, 0.49)
0.88
(0.64,
0.99)
0.9
(0.73,
0.98)
15
3
2
26
Hip
3.36
(1.47,
7.67)
0.26
(0.07, 0.93)
0.8
(0.44,
0.97)
0.76
(0.53,
0.92)
8
5
2
16
0.99
(0.94,
1.05)
1.72
(0.04,
84.59)
1
(0.88, 1)
0
(0, 0.07)
28
49
0
0
0.33
(0.07, 0.7)
0.86
(0.73,
0.94)
3
7
6
42
0.38
(0.09,
0.76)
0.91
(0.79,
0.98)
3
4
5
42
Mixed
(48
hip,
29
knee)
Mixed
(63
hip, 9
knee)
Tc-99m
Intraoperative
2.33
MDP 30.78
II
Levitsky 58*
cultures and
(0.74,
phase bone
(0.48, 1.25)
gross sepsis
7.37)
scintigraphy
Tc-99m
Mixed
MDP 34.31
Intraoperative
0.68
(63
phase bone
(1.18,
cultures and
II
Levitsky 54*
(0.4, 1.18)
scintigraphy
hip, 9
15.75)
gross sepsis
knee)
and plain
radiographs
*Analysis excludes 14 indeterminate results (positive cultures or sepsis, but not both)
TP FP FN TN
144
v0.1 03.25.10
Table 58. Other Nuclear Imaging tests
Level of
Evidence
I
II
Author
Klett
Bernay
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
N
Test
Reference
Standard
28
Antigranulocyte
antibody BW
250/183
scintigraphy
Histology
Knee
4.41
(1.74,
11.19)
0.05
(0, 0.7)
1
(0.75, 1)
0.8
(0.52,
0.96)
13
3
0
12
31
Tc-99m
nanocolloid
scintigraphy
Pathological
and gross
operative
findings
Hip
6
(2.28,
15.82)
0.05
(0, 0.82)
1
(0.69, 1)
0.86
(0.64,
0.97)
10
3
0
18
TP FP FN TN
145
v0.1 03.25.10
RECOMMENDATION 10
We are unable to recommend for or against computed tomography (CT) or magnetic
resonance imaging (MRI) as a diagnostic test for periprosthetic joint infection.
Strength of Recommendation: Inconclusive
Rationale
Computed Tomography (CT)
One included study indicated that some CT findings are possibly useful in the diagnosis
of periprosthetic infection, but more study is needed (range of positive LR: 0.3-46; range
of negative LR: 0.04-1.3).19 The evidence indicates that CT may be a good “rule in” test
but not as good a “rule out” test. This evidence is insufficient and does not allow a
recommendation for or against the use of this modality.
Magnetic Resonance Imaging (MRI)
There is insufficient evidence to address the diagnostic efficacy of MRI for diagnosing
periprosthetic infections. Based on the lack of evidence, we cannot recommend for or
against the use of MRI.
Supporting Evidence
CT: We included one study of hip patients with reliable data which examined computed
tomography (CT).19 Of the findings on CT that were studied, fluid collections in muscles
and perimuscular fat, joint distention, and soft-tissue abnormalities each produced
statistically significant positive and negative likelihood ratios. Findings of periostitis and
fluid-filled bursae each produced a statistically significant positive likelihood ratio. The
other findings did not produce statistically significant results. The results are presented in
Table 62.
No MRI studies met the inclusion criteria for this recommendation.
SUMMARY OF EVIDENCE
Table 59. CT and MRI Summary of Evidence
Test
Number
of
Studies
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
CT imaging –
various measures
(range)
1
0.29 – 45.7
0.04 – 1.28
0.08 - 1
0.3 - 1
146
v0.1 03.25.10
EXCLUDED ARTICLES
Author
Title
Reason for
Exclusion
Cooper, et al.
2008
Magnetic Resonance Imaging in the Diagnosis and
Management of Hip Pain After Total Hip Arthroplasty
<25 patients
Reinus, et al.
1996
Evaluation of femoral prosthetic loosening using CT
imaging
<25 patients
Sofka, et al.
2003
Magnetic resonance imaging of total knee arthroplasty
Insufficient
Data
147
v0.1 03.25.10
avoided
described
result(s) reported
STUDY QUALITY
Table 61. Study Quality - CT
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
● = Yes
○ = No
? = Unclear
Author
N
Cyteval 65
Cyteval 65
Cyteval 65
Cyteval 65
Index Test
CT asymmetric
position of
femoral head
CT - bone
abnormalities
(focal or
nonfocal low
attenuation,
periostitis)
CT - fluid
collections in
muscles and
perimuscular
fat
CT - fluidfilled bursae
Level of
Evidence
148
v0.1 03.25.10
avoided
described
result(s) reported
Table 61. Study Quality – CT (Continued)
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
● = Yes
○ = No
? = Unclear
Author
N
Cyteval 65
Cyteval 65
Cyteval 65
Cyteval 65
Cyteval 65
Cyteval 65
Cyteval 65
Index Test
- greater
trochanter
- iliopsoas
CT - focal
low
attenuation
CT - joint
distention
CT nonfocal low
attenuation
CT periostitis
CT - softtissue
abnormalities
Level of
Evidence
149
v0.1 03.25.10
STUDY RESULTS
Figure 20. CT Imaging Results - Likelihood Ratios
StudyId
StudyId
Cyteval - focal low attenuation
Cyteval - focal low attenuation
Cyteval - nonfocal low attenuation
Cyteval - nonfocal low attenuation
Cyteval - joint distention
Cyteval - joint distention
Cyteval - soft-tissue abnormalities
Cyteval - soft-tissue abnormalities
Cyteval - fluid collections
Cyteval - fluid collections
Cyteval - fluid-filled bursae
Cyteval - fluid-filled bursae
Cyteval - fluid bursae - greater trochanter
Cyteval - fluid bursae - greater trochanter
Cyteval - fluid bursae - iliopsoas
Cyteval - fluid bursae - iliopsoas
1 2 5 10
0 .1 .2
.5
1
DLR NEGATIVE
DLR POSITIVE
150
v0.1 03.25.10
Table 62. CT Imaging
Level of
Evidence
Author
N
I
Cyteval 65
I
Cyteval 65
I
Cyteval 65
I
Cyteval 65
I
Cyteval 65
I
Cyteval 65
I
Cyteval 65
Test
CT asymmetric
position of
femoral head
CT periostitis
- iliopsoas
CT - focal
low
attenuation
- greater
trochanter
CT nonfocal low
attenuation
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
Reference
Standard
Joint
Positive
Likelihood
Ratio
(95% CI)
Intraoperative
Cultures (≥2)
Hip
0.29
(0.04, 2.02)
1.28
(1.01, 1.63)
0.08
(0, 0.38)
0.72
(0.58, 0.83)
1
15
11
38
Intraoperative
Cultures (≥2)
Hip
20.77
(1.06, 407)
0.82
(0.62, 1.06)
0.17
(0.02, 0.48)
1
(0.93, 1)
2
0
10
53
Intraoperative
Cultures (≥2)
Hip
2.65
(0.73, 9.6)
0.83
(0.59, 1.16)
0.25
(0.05, 0.57)
0.91
(0.79, 0.97)
3
5
9
48
Intraoperative
Cultures (≥2)
Hip
1.47
(0.57, 3.78)
0.86
(0.56, 1.32)
0.33
(0.1, 0.65)
0.77
(0.64, 0.88)
4
12
8
41
Intraoperative
Cultures (≥2)
Hip
17.67
(2.16, 144)
0.68
(0.45, 1.02)
0.33
(0.1, 0.65)
0.98
(0.9, 1)
4
1
8
52
Intraoperative
Cultures (≥2)
Hip
0.88
(0.43, 1.83)
1.1
(0.64, 1.9)
0.42
(0.15, 0.72)
0.53
(0.39, 0.67)
5
25
7
28
Intraoperative
Cultures (≥2)
Hip
3.68
(1.34,
10.08)
0.66
(0.4, 1.07)
0.42
(0.15, 0.72)
0.89
(0.77, 0.96)
5
6
7
47
TP FP FN TN
151
v0.1 03.25.10
Table 62. CT Imaging (Continued)
Level of
Evidence
Author
N
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
Intraoperative
Cultures (≥2)
Hip
45.69
(2.69, 775)
0.58
(0.37, 0.93)
0.42
(0.15,
0.72)
1
(0.93, 1)
5
0
7
53
1.07
(0.74, 1.56)
0.83
(0.29, 2.4)
0.3
(0.18,
0.44)
9
37
3
16
0.96
(0.87, 1)
10
2
2
51
0.87
(0.75,
0.95)
12
7
0
46
Test
Reference
Standard
I
Cyteval 65
CT - fluid
collections in
muscles and
perimuscular
fat
I
Cyteval 65
CT - bone
abnormalities
Intraoperative
Cultures (≥2)
Hip
I
Cyteval 65
CT - joint
distention
Intraoperative
Cultures (≥2)
Hip
I
Cyteval 65
CT - softtissue
abnormalities
Intraoperative
Cultures (≥2)
Hip
22.08
(5.54,
88.03)
6.92
(3.53,
13.57)
0.17
(0.05, 0.61)
0.04
(0, 0.68)
0.75
(0.43,
0.95)
0.83
(0.52,
0.98)
1
(0.74, 1)
TP FP FN TN
152
v0.1 03.25.10
RECOMMENDATION 11
We recommend against the use of intraoperative Gram stain to rule out periprosthetic
joint infection.
Rationale
Our systematic review included three studies of Gram stain in the diagnosis of
periprosthetic joint infection.3, 78, 100 Negative likelihood ratios suggest this is not a good
“rule out” test (values >0.5). Comparatively, negative likelihood ratios for synovial fluid
white blood cell count and differential tests (Recommendation 4) are much lower (<0.1).
Thus, Gram stain is not a useful test for ruling out periprosthetic infection.
Supporting Evidence
Three included studies addressed the diagnostic utility of intraoperative Gram stains (one
hip, one knee, one hip and knee).3, 78, 100 Data from the knee study were of moderate
reliability, while the data from the other two studies were reliable. The test is fairly good
at ruling in infection (positive likelihood ratios greater than 10) but not as good at ruling
out infection (negative likelihood ratios greater than 0.5). Results are summarized in
Table 63.
SUMMARY OF EVIDENCE
Table 63. Gram Stain Summary of Evidence
Test
Number
of Studies
Positive
Likelihood
Ratio (95%
CI)
Negative
Likelihood
Ratio (95%
CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
Gram Stain
(range)
3
10.8 – 42.3
0.56 – 0.83
0.19 – 0.44
0.97 -1
*Range presented because fewer than four studies
153
v0.1 03.25.10
EXCLUDED ARTICLES
Author
Atkins, et al.
1998
Title
Prospective evaluation of criteria for microbiological diagnosis of prosthetic-joint infection
at revision arthroplasty. The OSIRIS Collaborative Study Group
Not best available
evidence
Barrack, et al.
1997
Not best available
evidence
Chimento, et al.
1996
Gram stain detection of infection during revision arthroplasty
Not best available
evidence
Della Valle, et al.
1999
The role of intraoperative Gram stain in revision total joint arthroplasty
>10% prostheses
already removed
Ghanem, et al.
2009
Periprosthetic infection: where do we stand with regard to Gram stain?
Not best available
evidence
Ko, et al.
2005
The role of intraoperative frozen section in decision making in revision hip and knee
arthroplasties in a local community hospital
Not best available
evidence
Kraemer, et al.
1993
Bone scan, gallium scan, and hip aspiration in the diagnosis of infected total hip
arthroplasty
Not best available
evidence
Spangehl, et al.
1999
Not best available
evidence
154
v0.1 03.25.10
N
Index Test
Level of
Evidence
avoided
described
result(s) reported
Author
● = Yes
○ = No
? = Unclear
STUDY QUALITY
Table 65. Gram Stain - Quality
Spangehl
Banit
Banit
202
63
55
Gram stain
Gram stain
Gram stain
I
I
I
?
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
?
?
?
●
●
●
●
●
●
●
●
●
●
●
Parvizi
70
Gram stain tissue
II
●
●
●
●
●
●
●
○
○
?
?
●
●
●
Parvizi
70
Gram stain fluid
II
●
●
●
●
●
●
●
○
○
?
?
●
●
●
155
v0.1 03.25.10
STUDY RESULTS
Figure 21. Gram Stain Results - Likelihood Ratios
StudyId
StudyId
Spangehl
Spangehl
Banit
Banit
Parvizi - tissue
Parvizi - tissue
Parvizi - fluid
Parvizi - fluid
1
2
5 10
.1 .2
DLR POSITIVE
.5
1
DLR NEGATIVE
156
v0.1 03.25.10
Table 66. Intraoperative Gram Stain Results
Level of
Evidence
I
Author
Test
Reference Standard
Joint
Positive
Likelihood
Ratio
(95% CI)
Gram
stain
At least 1 of: 1)open
wound or sinus
communicating with
the joint 2)purulent
3)positive
investigations in a
minumum of 3 of the
following: ESR >30
mm/h, CRP
>10mg/L,
preoperative
aspiration ≥1 positive
culture, frozen
section >5 PMNs/hpf,
>1/3 positive cultures
Hip
10.8
(2.74, 42.6)
N
Spangehl 202
I
Banit
63
Gram
stain
Intraoperative
cultures
Hip
I
Banit
55
Gram
stain
Intraoperative
cultures
Knee
39.75
(2.29,
689.8)
42.3
(2.47,
724.7)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
0.83
(0.69, 0.99)
0.19
(0.06,
0.38)
0.98
(0.95, 1)
5
3
22
172
1
(0.93, 1)
4
0
7
52
1
(0.92, 1)
4
0
5
46
0.63
(0.41, 0.98)
0.56
(0.32, 0.97)
0.36
(0.11,
0.69)
0.44
(0.14,
0.79)
TP FP FN
TN
157
v0.1 03.25.10
Table 66. Intraoperative Gram Stain Results (Continued)
Level of
Evidence
Author
N
Test
II
Parvizi
70
Gram
stain tissue
II
Parvizi
70
Gram
stain fluid
Reference Standard
at least 3 of: 1)CRP
>1mg/dL 2)ESR
>30mm/hr 3)positive
joint aspiration
culture 4)purulent
intraoperative tissue
appearance 5)positive
at least 3 of: 1)CRP
>1mg/dL 2)ESR
>30mm/hr 3)positive
joint aspiration
culture 4)purulent
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio (95%
CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
Knee
13.6
(0.82,
226.8)
0.8
(0.68, 0.95)
0.21
(0.09, 0.36)
1
(0.89, 1)
8
0
31
31
Knee
11.13
(1.55, 80.1)
0.66
(0.52, 0.85)
0.36
(0.21, 0.53)
0.97
(0.83, 1)
14
1
25
30
TP FP FN TN
158
v0.1 03.25.10
RECOMMENDATION 12
We recommend the use of frozen sections of peri-implant tissues in patients who are
undergoing reoperation for whom the diagnosis of periprosthetic joint infection has not
been established or excluded.
Rationale
Eight Level I studies were identified that evaluated the use of frozen sections to help
diagnose peri-implant infection.3, 21, 30, 32, 54, 59, 75, 96 Three studies excluded patients with
known underlying inflammatory arthropathy.30, 54, 96
Six of the eight studies used intraoperative cultures, while two studies used a combination
of test results as the gold standard for diagnosis against which the frozen sections were
compared. All studies based the histologic diagnosis of probable infection on the tissue
concentration of acute inflammatory cells, usually defined by two variables: 1) the
number of neutrophils in a high magnification (400X) microscopic field, and 2) the
minimum number of fields containing that concentration of neutrophils. At least three
studies excluded neutrophils entrapped in superficial fibrin.
Four studies used 10 or more neutrophils per high power field, and three of the four
required 10 more neutrophils in at least 5 fields. The remaining study required 10 or more
neutrophils in any given area. Our meta-analysis of these studies indicated that frozen
section is a very good “rule in” test (i.e., a positive result has a high likelihood of
infection; LR+: 23), but is a relatively low value “rule out” test (i.e. a negative result does
not have a high likelihood of absent infection; LR-: 0.23).
Four other studies used 5 or more neutrophils per high power field; several of these
specified at least 5 microscopic fields but the other studies did not. Meta-analysis
indicated that when compared to a 10 PMN/HPF criterion this lower inflammation
threshold may have similar sensitivity, but slightly lower specificity (i.e. a higher
frequency of false positive results).
There is insufficient information to distinguish 5 from 10 neutrophils per high power
field as the best threshold needed for diagnosis. Insufficient information is available to
determine the efficacy of frozen sections in patients with an underlying inflammatory
arthropathy.
159
v0.1 03.25.10
Supporting Evidence
We included eight studies with reliable data (two hip, one knee, two each, three mixed)
that addressed the diagnostic utility of frozen sections.3, 21, 30, 32, 54, 59, 75, 96 Meta-analysis
of these studies indicated between-study heterogeneity (I2=64%), possibly due to one
study which did not have a quantitative definition of infection seen on frozen section.30
Four studies used 10 or more neutrophils in five fields as a threshold. Meta-analysis of
these latter studies indicated that frozen section using this threshold was a very good
“rule in” test (positive LR = 23.4) and not as good as a “rule out” test (negative LR =
0.23). Four studies used a threshold of 5 PMN/HPF; meta-analysis of these studies
indicated a moderately good “rule in” test and not as good of a “rule out” test (positive
LR = 9.1, negative LR = 0.22). Five studies reported sampling suspicious-appearing sites,
and three reported excluding the histology of fibrin.
SUMMARY OF EVIDENCE
Table 67. Frozen Section Summary of Evidence
Test
Frozen section threshold of 10
PMN in 5 HPF
2
(I =0%)
Frozen section threshold of 5
PMN/HPF
2
(I =0%)
Number
of
Studies
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
4
23.4
(11.7, 47.1)
0.23
(0.14, 0.36)
0.78
(0.66, 0.86)
0.97
(0.94, 0.98)
4
9.1
(4.8, 17.2)
0.22
(0.13, 0.36)
0.80
(0.68, 0.88)
0.91
(0.84, 0.95)
160
v0.1 03.25.10
EXCLUDED ARTICLES
Author
Abdul-Karim, et al.
1998
Title
Frozen section biopsy assessment for the presence of polymorphonuclear leukocytes in
patients undergoing revision of arthroplasties
Not best available
evidence
Athanasou, et al.
1995
Diagnosis of infection by frozen section during revision arthroplasty
Not best available
evidence
Bori, et al.
2006
Low sensitivity of histology to predict the presence of microorganisms in suspected aseptic
loosening of a joint prosthesis
Not best available
evidence
Charosky, et al.
1973
Total hip replacement failures. A histological evaluation
<25 patients
Della Valle, et al.
1999
Analysis of frozen sections of intraoperative specimens obtained at the time of reoperation
after hip or knee resection arthroplasty for the treatment of infection
>10% prostheses
already removed
Fehring, et al.
1996
Not best available
evidence
Feldman, et al.
1995
Not best available
evidence
Kanner, et al.
2008
Reassessment of the usefulness of frozen section analysis for hip and knee joint revisions
Not best available
evidence
Kataoka, et al.
2002
An assessment of histopathological criteria for infection in joint arthroplasty in rheumatoid
synovium
Not relevant - not
specific to revision
surgery
Mirra, et al.
1976
The pathology of the joint tissues and its clinical relevance in prosthesis failure
Not best available
evidence
Mirra, et al.
1982
The pathology of failed total joint arthroplasty
Not best available
evidence
161
v0.1 03.25.10
Author
Title
Musso, et al.
2003
Role of frozen section histology in diagnosis of infection during revision arthroplasty
>10% prostheses
already removed
Pons, et al.
1999
Rosas, et al.
1998
Spangehl, et al.
1999
Not best available
evidence
<25
patients/insufficient
data
Not best available
evidence
Wong, et al.
2005
Intraoperative frozen section for detecting active infection in failed hip and knee
arthroplasties
Not best available
evidence
162
v0.1 03.25.10
avoided
described
result(s) reported
STUDY QUALITY
Table 69. Frozen Section - Quality
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
I
●
●
●
●
●
●
●
●
●
●
?
?
●
●
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
● = Yes
○ = No
? = Unclear
Author
N
Banit
63
Banit
55
Banit
121
Della
Valle
94
Fehring
97
Frances
Borrego
83
Index Test
Frozen section: >10 PMNs/high
power field in any of the sampled
areas
Frozen section: >10 PMNs/high
power field in any of the sampled
areas
Frozen section: >5 PMNs/high power
field in any of the sampled areas
Frozen section: avg. of >10 PMN
seen within tissue (not fibrin) in the 5
most cellular fields seen
Frozen section: acute inflammation
characterized by the presence of
PMNs (specific criteria of number
per field not established)
Frozen section: >10 PMNs/hpf in 5
fields
Level of
Evidence
163
v0.1 03.25.10
avoided
described
result(s) reported
Table 69. Frozen Section – Quality (Continued)
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
I
●
●
●
●
●
●
●
●
●
●
●
?
●
●
I
●
●
●
●
●
●
●
●
●
●
●
?
●
●
I
●
●
●
●
●
●
●
●
●
●
●
●
●
●
I
●
●
●
●
●
●
●
●
●
?
?
●
●
●
● = Yes
○ = No
? = Unclear
Author
N
Frances
Borrego
Ko
40
Lonner
175
Lonner
175
Nunez
136
Schinsky
201
63
Index Test
Frozen section: >10 PMNs/hpf in
5 fields
Frozen section: >5 PMNs/HPF
Frozen section: ≥10PMNs/hpf in
5 fields
Frozen section: ≥5 PMNs/hpf in
5 fields
Frozen section: ≥5 PMNs/hpf
(looked at 10 fields)
Frozen section: avg. of >10PMN
in the 5 most cellular HPF
Level of
Evidence
164
v0.1 03.25.10
STUDY RESULTS
Figure 22. Frozen Section Meta-Analysis – Threshold of 10 PMN in 5 Fields
StudyId
StudyId
Frances Borrego
Frances Borrego
Lonner
Lonner
Della Valle
Della Valle
Schinsky
Schinsky
COMBINED
COMBINED
1
2
5
10
.1
DLR POSITIVE
.2
.5
1
DLR NEGATIVE
Figure 23. Frozen Section Meta-Analysis – Threshold of 5 PMN/HPF
StudyId
StudyId
Banit
Banit
Lonner
Lonner
Ko
Ko
Nunez
Nunez
COMBINED
COMBINED
1
2
5
10
.1
DLR POSITIVE
.2
.5
1
DLR NEGATIVE
165
v0.1 03.25.10
Figure 24. Frozen Section Results - Likelihood Ratios – Mixed Thresholds
StudyId
StudyId
Lonner
Lonner
Della Valle
Della Valle
Schinsky
Schinsky
Frances Borrego
Frances Borrego
Banit
Banit
Nunez
Nunez
Ko
Ko
Fehring
Fehring
1
2
5 10
.1 .2
DLR POSITIVE
.5
1
DLR NEGATIVE
166
v0.1 03.25.10
Table 70. Frozen Section Results
Level of
Evidence
Author
N
I
Banit
63
I
Frances
Borrego
83
I
Schinsky
201
Test
Frozen
Section
(>10
PMNs/HPF
in any of the
sampled
areas)
Frozen
Section
(>10
PMNs/HPF
in 5 fields)
Frozen
Section
(avg. of >10
PMNs in the
5 most
cellular
HPF)
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
Intraoperative
Cultures
Hip
5.91
(1.88,
18.52)
0.59
(0.34, 1.02)
0.45
(0.17,
0.77)
0.92
(0.81,
0.98)
5
4
6
48
Intraoperative
Cultures
Hip
76
(4.45,
1299.33)
0.5
(0.26, 0.97)
0.5
(0.16,
0.84)
1
(0.95, 1)
4
0
4
75
At least 2 of: 1)a
positive
intraoperative
culture (on solid
media) 2)gross
purulence 3)final
histopathology
(avg. of >10
PMNs in the 5
most cellular
HPF)
Hip
11.8
(6.14,
22.67)
0.29
(0.19, 0.45)
0.73
(0.59,
0.84)
0.94
(0.89,
0.97)
40
9
15
137
Reference
Standard
TP FP FN
TN
167
v0.1 03.25.10
Table 70. Frozen Section Results (Continued)
Level of
Evidence
I
I
Author
Nunez
Banit
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
0.16
(0.08,
0.33)
0.86
(0.73,
0.94)
0.87
(0.79,
0.94)
42
11
7°
76
0.05
(0, 0.79)
1
(0.66, 1)
0.96
(0.85,
0.99)
9
2
0
44
N
Test
Reference
Standard
136
Frozen
Section (≥5
PMN/HPF;
looked at 10
fields)
Intraoperative
Cultures
Hip
6.78
(3.86,
11.92)
55
Frozen
Section
(>10
PMNs/HPF
in any of the
sampled
areas)
Intraoperative
Cultures
Knee
17.86
(5.3,
60.16)
Specificity
TP FP FN
(95% CI)
TN
168
v0.1 03.25.10
Level of
Evidence
I
I
I
Author
Della
Valle
Frances
Borrego
Banit
63
63
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Knee
23.27
(5.95,
91.05)
0.13
(0.06,
0.29)
0.88
(0.74,
0.96)
0.96
(0.87, 1)
36
2
5
51
Intraoperative
Cultures
Knee
6.5
(2.46,
17.16)
0.37
(0.21,
0.66)
0.67
(0.45,
0.84)
0.90
(0.76,
0.97)
16
4
8
35
Intraoperative
Cultures
Mixed
(63 hip,
55 knee,
3
shoulder)
4.17
(2.42,
7.16)
0.40
(0.22,
0.73)
0.67
(0.43,
0.85)
0.84
(0.75,
0.910
14
16
7
84
Test
Frozen
Section
(avg. of >10
PMNs in the
5 most
cellular
HPF)
At least 2 of 3
positive
intraoperative
cultures on
solid media or
2 of following:
1)one positive
culture 2)final
histopathology
consistent with
infection
3)gross
purulence seen
at time of
revision
N
94
Joint
Positive
Likelihood
Ratio
(95% CI)
Reference
Standard
Frozen
Section
(>10
PMNs/hpf
in 5 fields)
Frozen
Section (>5
PMNs/HPF
in any of the
sampled
areas)
Specificity
TP FP FN
(95% CI)
TN
169
v0.1 03.25.10
Level of
Evidence
I
I
I
I
Author
Fehring
Ko
Lonner
Lonner
Joint
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
TP FP FN
(95% CI)
N
Test
Reference
Standard
97
Frozen
Section
(Presence of
PMNs (no
specific
criteria of
number per
field)
Intraoperative
Cultures
Mixed
1.74
(0.43,
7.03)
0.91
(0.69,
1.22)
0.18
(0.02,
0.52)
0.90
(0.81,
0.95)
2
9*
9
77
40
Frozen
Section (>5
PMNs/HPF)
Intraoperative
Cultures
Mixed
(34 hip,
6 knee)
20.67
(2.85,
150.1)
0.34
(0.14,
0.87)
0.67
(0.3, 0.93)
0.97
(0.83, 1)
6
1
3
30
175
Frozen
Section
(≥10
PMN/HPF
in 5 fields)
Intraoperative
Cultures
Mixed
(142 hip,
33 knee)
65.7
(16.4, 264)
0.16
(0.06,
0.45)
0.84
(0.60,
0.97)
0.99
(0.95, 1)
16
2
3
154
175
Frozen
Section (≥5
PMN/HPF
in 5 fields)
Intraoperative
Cultures
Mixed
(142 hip,
33 knee)
18.8
(8.87,
39.7)
0.17
(0.06,
0.47)
0.84
(0.60,
0.97)
0.96
(0.91,
0.98)
16
7
3
149
TN
°Three of seven positive cultures considered possible contaminants due to negative clinical and intraoperative findings
*Study noted 6 cases with negative cultures but high clinical suspicion of infection; 3 cases with indeterminate results not included
170
v0.1 03.25.10
RECOMMENDATION 13
We recommend that multiple cultures be obtained at the time of reoperation in patients
being assessed for periprosthetic joint infection.
Rationale
Four Level I studies compared the effects of using one as opposed to more than one
positive culture as a threshold for diagnosing infection, with histology of peri-implant
tissue as the gold standard.2, 94, 104, 105 Two of these studies obtained at least three cultures
per patient and two of these studies obtained at least two cultures per patient. Compared
to histology, more than one positive culture result had a higher positive likelihood ratio
for diagnosing infection than a single positive culture result.
Assessing infection using multiple cultures increases the chances of identifying infection.
Cultures are easily performed during the procedure and provide reliable results as
indicated by the postive likelihood ratio. Obtaining more than one culture decreases the
likelihood of false negative result and may assist the clinician in clarifying a result that
may be deemed a false positive based on the results of other tests.
Supporting Evidence
Four studies presented reliable data on the effects of using one or more than one positive
culture as a threshold for infection.2, 94, 104, 105 In these studies, authors sampled from the
“most suspicious areas” or “areas that appear to be most infected or inflamed”. In these
studies, cultures were compared to histologic findings or a combination of histologic
findings, visible purulence, and a sinus tract communicating with the prosthesis. There
was between-study heterogeneity in each category. Samples were taken for aerobic and
anaerobic culture in each study.
One study with moderately reliable data compared swab vs. tissue,99 and another study
with less reliable data compared fluid vs. tissue.78 In each study, the differences between
the two techniques were not statistically significant.
SUMMARY OF EVIDENCE
Table 71. Summary of Evidence
Test
Number
of
Studies
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Specificity
(95% CI)
4
2.87 – 8.1
0.09 – 0.29
0.73 – 0.94
0.67 – 0.91
4
11.5 – 76.6
0.25 – 0.47
0.54 – 0.77
0.93 – 0.99
Intraoperative
Cultures (≥1
positive culture) –
range
Intraoperative
Cultures (≥2
171
v0.1 03.25.10
positive cultures)
– range
*Range presented because meta-analysis indicated heterogeneity
172
v0.1 03.25.10
EXCLUDED ARTICLES
Author
Baker, et al.
1994
Title
Use of Sentinel blood culture system for analysis of specimens from potentially infected
prosthetic joints
Does not address
recommendation
Bare, et al.
2006
Preoperative evaluations in revision total knee arthroplasty
Not best available
evidence
Barrack, et al.
2007
The fate of the unexpected positive intraoperative cultures after revision total knee
arthroplasty
Not best available
evidence
Barrack, et al.
1993
The value of aspiration of the hip joint before revision total hip arthroplasty
Not best available
evidence
Berend, et al.
2007
Unexpected positive intraoperative cultures and gram stain in revision total hip
arthroplasty for presumed aseptic failure
Not best available
evidence
Cune, et al.
2008
A Superficial Swab Culture is Useful for Microbiologic Diagnosis in Acute Prosthetic
Joint Infections
Not best available
evidence
Duff, et al.
1996
Not best available
evidence
Dupont,
1986
Significance of operative cultures in total hip arthroplasty
Insufficient Data
Fehring, et al.
1996
Not best available
evidence
Feldman, et al.
1995
Not best available
evidence
Fitzgerald, et al.
1973
Bacterial colonization of wounds and sepsis in total hip arthroplasty
Does not address
recommendation
Ince, et al.
2004
Is 'aseptic' loosening of the prosthetic cup after total hip replacement due to nonculturable
bacterial pathogens in patients with low-grade infection?
<25 patients
173
v0.1 03.25.10
Author
Title
Levine, et al.
2001
Use of blood culture vial specimens in intraoperative detection of infection
<25 patients
Marculescu, et al.
2005
Prosthetic joint infection diagnosed postoperatively by intraoperative culture
Does not address
recommendation
Mehra, et al.
2006
Bacteriology swab in primary total hip arthroplasty-- does it have a role?
Does not address
recommendation
Mikkelsen, et al.
2006
Culture of multiple peroperative biopsies and diagnosis of infected knee arthroplasties
Not best available
evidence
Moojen, et al.
2007
Identification of orthopaedic infections using broad-range polymerase chain reaction and
reverse line blot hybridization
Not best available
evidence
Muller, et al.
2008
Not best available
evidence
Neut, et al.
2003
Detection of biomaterial-associated infections in orthopaedic joint implants
<25 patients
Padgett, et al.
1995
Efficacy of intraoperative cultures obtained during revision total hip arthroplasty
Not best available
evidence
Pandey, et al.
2000
Histological and microbiological findings in non-infected and infected revision
arthroplasty tissues. The OSIRIS Collaborative Study Group. Oxford Skeletal Infection
Research and Intervention Service
Not best available
evidence
Panousis, et al.
2005
Poor predictive value of broad-range PCR for the detection of arthroplasty infection in 92
cases
Not best available
evidence
Picado, et al.
2008
Accuracy of intraoperative cultures in primary total hip arthroplasty
Does not address
recommendation
Pipino, et al.
1989
Bacteriological and histological study of 40 loose cemented hip prostheses
Insufficient Data
174
v0.1 03.25.10
Author
Title
Pizzoferrato, et al.
1980
Microbiological investigation of 161 cases of hip endo-arthroprosthesis failure
Insufficient Data
Ringberg, et al.
1998
Bacteriologic evidence of infection caused by coagulase-negative staphylococci in total hip
replacement
Does not address
recommendation
Schinsky, et al.
2008
Perioperative testing for joint infection in patients undergoing revision total hip
arthroplasty
Not best available
evidence
Spangehl, et al.
1999
arthroplasty
Not best available
evidence
Tietjen, et al.
1977
The significance of intracapsular cultures in total hip operations
Not best available
evidence
175
v0.1 03.25.10
N
Index Test
avoided
described
result(s) reported
Author
Level of
Evidence
STUDY QUALITY
Table 73. Intraoperative Cultures - Quality
Atkins
297
Intraoperative Cultures (≥3)
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
Atkins
213
I
?
●
●
●
●
●
●
●
●
●
?
●
●
●
Atkins
239
I
?
●
●
●
●
●
●
●
●
●
?
●
●
●
Atkins
297
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
Atkins
213
I
?
●
●
●
●
●
●
●
●
●
?
●
●
●
Atkins
239
I
?
●
●
●
●
●
●
●
●
●
?
●
●
●
Atkins
297
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
Atkins
213
I
?
●
●
●
●
●
●
●
●
●
?
●
●
●
Atkins
239
I
?
●
●
●
●
●
●
●
●
●
?
●
●
●
Schafer
284
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
Schafer
284
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
● = Yes
○ = No
? = Unclear
Intraoperative Cultures (≥1, solid
or broth)
or broth)
or broth)
176
v0.1 03.25.10
avoided
described
result(s) reported
Index Test
Level of
Evidence
N
Table 73. Intraoperative Cultures – Quality (Continued)
78
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
78
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
331
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
331
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
III
●
●
●
●
●
●
○
●
●
●
?
●
●
●
III
●
●
●
●
●
●
○
●
●
●
?
●
●
●
● = Yes
○ = No
? = Unclear
Author
Trampuz
2006
Trampuz
2006
Trampuz
2007
Trampuz
2007
Intraoperative culture of tissue
(>1/3 of sample positive)
Intraoperative swab culture (>1/3
of samples positive)
Spangehl
180
Spangehl
168
Parvizi
70
Intraoperative fluid culture
IV
●
●
●
●
●
●
○
○
○
●
?
●
●
●
Parvizi
70
Intraoperative tissue culture
IV
●
●
●
●
●
●
○
○
○
●
?
●
●
●
177
v0.1 03.25.10
STUDY RESULTS
Figure 25. Intraoperative Cultures Results - Threshold of 1 vs. 2 Positive Cultures
StudyId
StudyId
Schafer - 1
Schafer - 1
Trampuz (2006) - 1
Trampuz (2006) - 1
Atkins - 1
Atkins - 1
Trampuz (2007) - 1
Trampuz (2007) - 1
Schafer - 2
Schafer - 2
Trampuz (2006) - 2
Trampuz (2006) - 2
Atkins - 2
Atkins - 2
Trampuz (2007) - 2
Trampuz (2007) - 2
1
2
5 10
.1
.2
.5
1
DLR NEGATIVE
DLR POSITIVE
Figure 26. Intraoperative Cultures Results - Tissue or Swab or Fluid
StudyId
StudyId
Spangehl - swab
Spangehl - swab
Spangehl - tissue
Spangehl - tissue
Parvizi - tissue
Parvizi - tissue
Parvizi - fluid
Parvizi - fluid
1 2
5 10
.1
DLR POSITIVE
.2
.5 1
DLR NEGATIVE
178
v0.1 03.25.10
Table 74. Overall and number of cultures results
Level of
Evidence
I
I
Author
Schafer
Trampuz
2006
78
Negative
Likelihood
Ratio
(95% CI)
Sensitivity
(95% CI)
Histology
Mixed
(145
hip,
139
knee)
2.87
(2.32,
3.56)
0.09
(0.04,
0.19)
At least 1 of:
1)visible
purulence of
synovial fluid
or area
surrounding the
prosthesis
2)acute
inflammation
on
histopathologic
exam of
permanent
periprosthetic
tissue sections
3)a sinus tract
communicating
with the
prosthesis
Mixed
(68
knee,
10
hip)
8.1
(3.41,
19.26)
0.28
(0.14,
0.55)
Intraoperative
Cultures (≥1)
Intraoperative
Cultures (≥1)
N
284
Joint
Positive
Likelihood
Ratio
(95% CI)
Reference
Standard
Test
Specificity
TP FP FN
(95% CI)
TN
0.94
(0.88,
0.98)
0.67
(0.6, 0.74)
98
59
6
121
0.75
(0.53, 0.9)
0.91
(0.8, 0.97)
18
5
6
49
179
v0.1 03.25.10
Table 74. Overall and number of cultures results (Continued)
Level of
Evidence
Author
N
Test
Reference
Standard
I
Atkins
(all)
297
Intraoperative
Cultures (≥1)
Histology
I
Atkins
(patients
with 3-6
samples)
213
Intraoperative
Cultures (≥1)
Histology
I
Atkins
(patients
operated
Intraoperative
239
on by
Cultures (≥1)
most
consistent
sureons)
Histology
Joint
Mixed
(253
hip,
44
knee)
Mixed
(253
hip,
44
knee)
Mixed
(253
hip,
44
knee)
Negative
Positive
TP FP
(95% CI) (95% CI)
Ratio
Ratio
(95% CI)
(95% CI)
FN
TN
4.33
(3.25,
5.78)
0.21
(0.11,
0.42)
0.83
(0.68,
0.93)
0.81
(0.75,
0.85)
34
49
7
207
4.01
(2.89,
5.56)
0.22
(0.1, 0.48)
0.83
(0.64,
0.94)
0.79
(0.73,
0.85)
24
38
5
146
4.37
(3.19,
5.98)
0.19
(0.08,
0.42)
0.85
(0.68,
0.95)
0.81
(0.75,
0.86)
28
40
5
166
180
v0.1 03.25.10
Level of
Evidence
I
I
Author
Trampuz
2007
Schafer
N
Test
Reference
Standard
Joint
At least 1 of:
1)visible
purulence of
synovial fluid
or area
surrounding
the prosthesis
2)acute
Mixed
(207
inflammation
Intraoperative
knee,
on
331
Cultures (≥1)
124
histopathologic
hip)
exam of
permanent
periprosthetic
tissue sections
3)a sinus tract
communicating
with the
prosthesis
Mixed
(145
Intraoperative
284
Histology
hip,
Cultures (≥2)
139
knee)
Negative
Positive
TP FP
(95% CI) (95% CI)
Ratio
Ratio
(95% CI)
(95% CI)
FN
TN
8.04
(5.33,
12.14)
0.29
(0.2, 0.42)
0.73
(0.62,
0.83)
0.91
(0.87,
0.94)
58
23
21
229
11.54
(6.61,
20.13)
0.25
(0.17,
0.35)
0.77
(0.68,
0.85)
0.93
(0.89,
0.97)
80
12
24
168
181
v0.1 03.25.10
Level of
Evidence
Author
I
Trampuz
2006
I
Atkins
(all)
N
Test
Reference
Standard
Joint
At least 1 of:
1)visible
purulence of
synovial fluid
or area
surrounding
the prosthesis
2)acute
Mixed
(68
inflammation
Intraoperative
knee,
on
78
Cultures (≥2)
10
histopathologic
hip)
exam of
permanent
periprosthetic
tissue sections
3)a sinus tract
communicating
with the
prosthesis
Mixed
(253
Intraoperative
297
Histology
hip,
Cultures (≥2)
44
knee)
Negative
Positive
TP FP
(95% CI) (95% CI)
Ratio
Ratio
(95% CI)
(95% CI)
FN
TN
29.25
(4.05, 211)
0.47
(0.3, 0.72)
0.54
(0.33,
0.74)
0.98
(0.9, 1)
13
1
11
53
25.87
(12.1,
55.1)
0.3
(0.19,
0.48)
0.71
(0.54,
0.84)
0.97
(0.94,
0.99)
29
7
12
249
182
v0.1 03.25.10
Level of
Evidence
Author
I
Atkins
(patients
with 3-6
samples)
I
Atkins
(patients
operated
Intraoperative
on by
239
Cultures (≥2)
most
consistent
sureons)
N
213
Test
Intraoperative
Cultures (≥2)
Negative
Positive
TP FP
(95% CI) (95% CI)
Ratio
Ratio
(95% CI)
(95% CI)
Reference
Standard
Joint
Histology
Mixed
(253
hip,
44
knee)
24.11
(9.76,
59.54)
0.35
(0.21,
0.59)
0.66
(0.46,
0.82)
0.97
(0.94,
0.99)
19
Histology
Mixed
(253
hip,
44
knee)
25.0
(11.1,
56.5)
0.28
(0.16,
0.49)
0.73
(0.54,
0.87)
0.97
(0.94,
0.99)
24
FN
TN
5
10
179
6
9
200
183
v0.1 03.25.10
Level of
Evidence
Author
I
Trampuz
2007
I
Atkins
(all)
N
Test
Reference
Standard
Joint
At least 1 of:
1)visible
purulence of
synovial fluid
or area
surrounding
the prosthesis
2)acute
Mixed
(207
inflammation
Intraoperative
knee,
on
331
Cultures (≥2)
124
histopathologic
hip)
exam of
permanent
periprosthetic
tissue sections
3)a sinus tract
communicating
with the
prosthesis
Mixed
(253
Intraoperative
297
Histology
hip,
Cultures (≥3)
44
knee)
Negative
Positive
TP FP
(95% CI) (95% CI)
Ratio
Ratio
(95% CI)
(95% CI)
FN
TN
250
76.6
(19.0, 308)
0.4
(0.3, 0.52)
0.61
(0.49,
0.72)
0.99
(0.97, 1)
48
2
31
168
(23.6,
1207)
0.34
(0.22,
0.52)
0.66
(0.49, 0.8)
1
(0.98, 1)
27
1
142 255
184
v0.1 03.25.10
Level of
Evidence
Author
I
Atkins
(patients
with 3-6
samples)
I
Atkins
(patients
operated
Intraoperative
on by
239
Cultures (≥3)
most
consistent
sureons)
N
213
Test
Intraoperative
Cultures (≥3)
Reference
Standard
Joint
Negative
Positive
TP FP
(95% CI) (95% CI)
Ratio
Ratio
(95% CI)
(95% CI)
Histology
Mixed
(253
hip,
44
knee)
114
(15.8, 823)
0.38
(0.24,
0.61)
0.62
(0.42,
0.79)
0.99
(0.97, 1)
18
Histology
Mixed
(253
hip,
44
knee)
144
(20.1,
1028)
0.3
(0.18,
0.51)
0.7
(0.51,
0.84)
1
(0.97, 1)
23
FN
TN
1
11
183
1
10
205
185
v0.1 03.25.10
Table 75. Tissue vs. Swab vs. Fluid
Level of
Evidence
III
Author
N
Test
Reference Standard
wound of sinus in
communication with
Intraoperative
Swab
least 3
Cultures
Spangehl 168
(>1/3 of
samples
aspiration with at least
positive)
1 positive culture,
frozen section with
>5PMN/HPF,
(>1/3 of cultures
positive)
Negative
Positive
TP FP FN
Joint
(95% CI) (95% CI)
Ratio
Ratio
(95% CI)
(95% CI)
Hip
115
(16.1, 829)
0.24
(0.1, 0.56)
0.76
(0.5, 0.93)
0.99
(0.96, 1)
13
1
4
186
v0.1 03.25.10
TN
150
Table 75. Tissue vs. Swab vs. Fluid (Continued)
Level of
Evidence
III
Author
N
Test
Reference Standard
wound of sinus in
communication with
Intraoperative
Tissue
least 3
Cultures
Spangehl 180
(>1/3 of
sample
aspiration with at least
positive)
1 positive culture,
frozen section with
>5PMN/HPF,
(>1/3 of cultures
positive)
Negative
Positive
TP FP FN
Joint
(95% CI) (95% CI)
Ratio
Ratio
(95% CI)
(95% CI)
Hip
30.6
(12.8,
73.1)
0.06
(0.01,
0.39)
0.94
(0.73, 1)
0.97
(0.93,
0.99)
17
5
1
187
v0.1 03.25.10
TN
157
Table 75. Tissue vs. Swab vs. Fluid (Continued)
Level of
Evidence
Author
N
Test
IV
Parvizi
70
Intraoperative
Tissue
Culture
IV
Parvizi
70
Intraoperative
Fluid Culture
Reference Standard
At least 3 of: 1)CRP
>1mg/dL 2)ESR
>30mm/hr 3)positive
joint aspiration culture
4)purulent
At least 3 of: 1)CRP
>1mg/dL 2)ESR
>30mm/hr 3)positive
joint aspiration culture
4)purulent
Negative
Positive
TP FP FN
Joint
(95% CI) (95% CI)
Ratio
Ratio
(95% CI)
(95% CI)
Knee
53.6
(3.41, 841)
0.17
(0.08,
0.33)
0.85
(0.69,
0.94)
1
(0.89, 1)
33
0
6
31
Knee
27.8
(4.03, 191)
0.11
(0.04,
0.27)
0.9
(0.76,
0.97)
0.97
(0.83, 1)
35
1
4
30
188
TN
v0.1 03.25.10
RECOMMENDATION 14
We recommend against initiating antibiotic treatment in patients with suspected
periprosthetic joint infection until after cultures from the joint have been obtained.
Rationale
One Level I study addressed whether administration of antibiotic therapy prior to
obtaining cultures from the joint affected the sensitivity of the cultures in diagnosing
periprosthetic infections.105 The study found a false negative rate of 55% in patients
receiving antibiotics within the previous 14 days compared to 23% in patients not
receiving antibiotics during the same time period. The difference was statistically
significant. Hence, there is a concern that antibiotics can interfere with isolation of the
infecting organism leading to confusion regarding the diagnosis or inability to use
organism specific antibiotics subsequently when infection is confirmed. Thus,
administration of oral or intravenous antibiotics to patients with suspected diagnosis of
periprosthetic joint infection is discouraged, until aspiration of the joint is performed or
samples for culture are obtained.
The finding of only one Level I study supporting this recommendation would be
evaluated as moderate strength. However, because of the severity of the potential harm to
the patient in getting a false negative culture result, the strength of the recommendation
was elevated to strong.
Supporting Evidence
One included study with reliable data addressed whether antibiotic therapy decreases the
sensitivity of intraoperative cultures in diagnosing periprosthetic infection.105 The group
of patients who had received antimicrobial therapy within 14 days of surgery had a
statistically significantly higher rate of false-negative culture results than those who had
not. In this study, a positive result was defined as growth from at least two specimens.
189
v0.1 03.25.10
EXCLUDED ARTICLES
Table 76. Excluded Articles - Recommendation14
Author
Barrack, et al.
1997
Title
<25 patients/arm
Datz, et al.
1986
Not relevant - not
specific to pji
Spangehl, et al.
1999
<25 patients/arm
Spangehl, et al.
1999
arthroplasty
<25 patients/arm
Trampuz, et al.
2006
<25 patients
190
v0.1 03.25.10
Author
N
Index Test
Level of
Evidence
described
result(s) reported
● = Yes
○ = No
? =Unclear
STUDY QUALITY
Table 77. Preoperative Antibiotic Therapy - Quality
Trampuz
78
Intraoperative
Cultures (≥2)
I
●
●
●
●
●
●
●
●
●
●
?
●
●
●
191
v0.1 03.25.10
STUDY RESULTS
Level of
Evidence
I
Author
Trampuz
N
79
Joint
Mixed
Reference Standard
False Negatives
Risk Ratio
pvalue
At least 1 of: 1)visible purulence of synovial
fluid or area surrounding the prosthesis
2)acute inflammation on histopathologic
exam of permanent periprosthetic tissue
sections 3)a sinus tract communicating with
the prosthesis
Antibiotics within 14 days: 55%
No antibiotics within 14 days: 23%
2.38
(1.26,
4.51)
0.004
192
v0.1 03.25.10
RECOMMENDATION 15
We suggest that prophylactic pre-operative antibiotics not be withheld in patients at lower
probability for periprosthetic infection and those with an established diagnosis of
periprosthetic joint infection who are undergoing reoperation.
Rationale
Two Level II studies and two joint registry studies found that the administration of
perioperative antibiotics significantly decreased the risk of postoperative infection.14, 26,
28, 43
These studies however, do not address whether or not the administration of
preoperative antibiotics interfere with intraoperative cultures. One Level III study did not
find a significant difference in the false negative rate of intraoperative knee cultures in
patients receiving perioperative antibiotic prophylaxis (12.5 vs. 8.1%; p=0.34).34
Patients who contract periprosthetic infection face catastrophic complications including
additional surgery, increased cost and prolonged treatment, as well as possible permanent
loss of the prosthesis. The important role of antibiotic prophylaxis in helping to prevent
these catastrophic events outweighs the potential risks.
Supporting Evidence
Two RCTs, neither specific to patients undergoing revision, compared preoperative
antibiotics to placebo.14, 26 Two joint registry studies, one of which was specific to
patients undergoing revision, compared antibiotic prophylaxis (systemic and/or cement)
to no antibiotic prophylaxis.28, 43 The two RCTs and one of the joint registry studies were
of hip patients; the other joint registry study was of knee patients. The studies’ results
indicated a higher risk of infection when antibiotics were not used. The results are
presented in Table 84 and Table 85.
One included study with moderately reliable data addressed whether administration of
preoperative antibiotics decreases the sensitivity of intraoperative cultures in diagnosing
periprosthetic infection.34 Among patients in whom the infecting organism had been
isolated from the preoperative aspiration, the rate of false-negative intraoperative culture
results was not statistically significantly different between the group of patients who had
received antibiotics and the group who had not.
193
v0.1 03.25.10
EXCLUDED ARTICLES
Author
Akre, et al.
2000
Title
Risk for gastric cancer after antibiotic prophylaxis in patients undergoing hip replacement
Does not address
recommendation
AlBuhairan, et al.
2008
Antibiotic prophylaxis for wound infections in total joint arthroplasty: a systematic review
Systematic review,
Bratzler, et al.
2004
Antimicrobial prophylaxis for surgery: An advisory statement from the national surgical
infection prevention project
Narrative review,
Chodak, et al.
1977
Use of systemic antibiotics for prophylaxis in surgery: a critical review
Systematic review,
de Lalla, et al.
1993
Regional and systemic prophylaxis with teicoplanin in monolateral and bilateral total knee
replacement procedures: study of pharmacokinetics and tissue penetration
Not best available
evidence
Ericson, et al.
1973
Cloxacillin in the prophylaxis of postoperative infections of the hip
Duplicate data
Eshkenazi, et al.
2001
Serum and synovial vancomycin concentrations following prophylactic administration in
knee arthroplasty
Not best available
evidence
Espehaug, et al.
1997
Antibiotic prophylaxis in total hip arthroplasty
Duplicate data
Gillespie, et al.
2001
Antibiotic prophylaxis for surgery for proximal femoral and other closed long bone
fractures
Does not address
recommendation
Glenny, et al.
1999
Antimicrobial prophylaxis in total hip replacement: a systematic review
Systematic review,
Hill, et al.
1981
Prophylactic cefazolin versus placebo in total hip replacement. Report of a multicentre
double-blind randomised trial
Duplicate data
Hughes, et al.
1979
Treatment of subacute sepsis of the hip by antibiotics and joint replacement. Criteria for
diagnosis with evaluation of twenty-six cases
Does not address
recommendation
194
v0.1 03.25.10
Author
Isacson, et al.
1984
Title
Renal impairment after high doses of dicloxacillin-prophylaxis in joint replacement
surgery
Does not address
recommendation
Johnson,
1987
Antibiotic prophylaxis with cefuroxime in arthroplasty of the knee
<25 patients
Klenerman, et al.
1991
Combined prophylactic effect of ultraclean air and cefuroxime for reducing infection in
prosthetic surgery
Not best available
evidence
Lidwell, et al.
1987
Ultraclean air and antibiotics for prevention of postoperative infection. A multicenter study
of 8,052 joint replacement operations
Duplicate data
Lidwell, et al.
1984
Infection and sepsis after operations for total hip or knee-joint replacement: influence of
ultraclean air, prophylactic antibiotics and other factors
Duplicate data
Lidwell, et al.
1982
Effect of ultraclean air in operating rooms on deep sepsis in the joint after total hip or knee
replacement: a randomised study
Not best available
evidence
Mannien, et al.
2006
Effect of optimized antibiotic prophylaxis on the incidence of surgical site infection
Not best available
evidence
Marotte, et al.
1987
Infection rate in total hip arthroplasty as a function of air cleanliness and antibiotic
prophylaxis. 10-year experience with 2,384 cementless Lord madreporic prostheses
Not best available
evidence
McQueen, et al.
1987
A comparison of systemic cefuroxime and cefuroxime loaded bone cement in the
prevention of early infection after total joint replacement
Does not address
recommendation
Mini, et al.
2001
Preliminary results of a survey of the use of antimicrobial agents as prophylaxis in
orthopedic surgery
Does not address
recommendation
Nelson, et al.
1993
A comparison of gentamicin-impregnated polymethylmethacrylate bead implantation to
conventional parenteral antibiotic therapy in infected total hip and knee arthroplasty
Does not address
recommendation
Nelson, et al.
1980
The effect of previous surgery, operating room environment, and preventive antibiotics on
postoperative infection following total hip arthroplasty
Not best available
evidence
Norden,
1983
A critical review of antibiotic prophylaxis in orthopedic surgery
Narrative review,
195
v0.1 03.25.10
Author
Parvizi, et al.
2008
Title
Duplicate Data
Schulitz, et al.
1980
The prophylactic use of antibiotics in alloarthroplasty of the hip joint for coxarthrosis. A
randomized study
Antibiotics not given
preoperatively
Van Kasteren, et al.
2007
Antibiotic prophylaxis and the risk of surgical site infections following total hip
arthroplasty: Timely administration is the most important factor
Does not address
recommendation
196
v0.1 03.25.10
Author
N
Index Test
Level of
Evidence
described
result(s) reported
● = Yes
○ = No
? =Unclear
STUDY QUALITY
Table 80. Preoperative Antibiotics - Diagnostic Study Quality
Ghanem
171
Intraoperative
Cultures (≥1)
III
?
●
●
●
●
●
○
●
●
●
○
●
●
●
197
v0.1 03.25.10
Level of
Evidence
Carlsson
Carlsson
Doyon
Doyon
Cloxacillin
Cloxacillin
Cefazolin
Cefazolin
Placebo
Placebo
Placebo
Placebo
171
118
2137
1069
II
II
II
II
Similar in Outcome at
Baseline
N
>80% Follow-Up
Control
Assessor Blind
Treatment
Subjects Blind
Author
Allocation Concealment
● = Yes
○ = No
? = Not Reported
Stochastic Randomization
Table 81. Preoperative Antibiotics - Randomized Trial Quality
?
?
?
?
○
○
●
●
●
●
●
●
?
?
○
○
○
○
●
○
●
●
●
●
Validated Data
>90% of patients captured
Control
N
Statistical Quality Control Measures
Performed
Ensures correct diagnosis
Treatment
Level of
Evidence
Population-Based Registry
Author
Mandatory Data Submission
Table 82. Preoperative Antibiotics - Joint Registry Quality
Engesaeter
Cephalosporin
or Penicillin
No
antibiotic
22170
II
○
●
●
●
●
●
Jamsen
Not specified
(most often
cefuroxime)
No
antibiotic
43149
II
●
●
○
●
?
●
● = Yes
○ = No
? = Not Reported
n/a = not applicable
198
v0.1 03.25.10
STUDY RESULTS
Level of
Evidence
III
Author
Ghanem
N
171
Joint
Reference Standard
False Negatives
Risk
Ratio
pvalue
Knee
Aspiration culture on
solid media, or on
liquid media if
positive, if CRP,
ESR, and aspirate
leukocyte cell count
and/or neutrophil
percentage were
elevated in presence
of intraoperative
purulent material
Antibiotics:
12.5%
No antibiotics:
8.1%
1.55
(0.63,
3.81)
0.34
Table 84. Relative Risk of Infection - Placebo vs. Preoperative Antibiotics
Relative
Risk*
(95%
CI)
∞ (no
infections
in
antibiotic
group)
7.2
(1.7,
30.5)
Level of
Evidence
Author
N
Joint
Duration
(years)
II
Carlsson
171
Hip
0.5
II
Carlsson
118
Hip
5
II
Doyon
2137
Hip
2
3.5
(1.7, 7.1)
II
Doyon
1069
Hip
5
4.9
(2.5, 9.6)
Positive
Likelihood
Ratio
(95% CI)
Negative
Likelihood
Ratio
(95% CI)
Number
Needed
to Treat
1.99
(1.71,
2.31)
0
22
2.03
(1.52,
2.71)
1.58
(1.34,
1.85)
1.73
(1.52,
1.97)
0.22
(0.06,
0.81)
0.44
(0.25,
0.76)
0.33
(0.18,
0.57)
5
43
14
* RR > 1 indicates greater risk in placebo group
199
v0.1 03.25.10
Table 85. Registry Data – Hazard Ratio of Revision due to Infection
Level of
Evidence
Author
II
Jamsen
(<25 patients in
the no antibiotic
group)
II
Engesaeter
N
2166
22170
Type of
Surgery
Revision
Primary
Joint
Adjusted Hazard Ratio*
Knee
systemic + cement: 1
systemic only:
2.1 (1.1, 3.9)
cement only:
1.9 (0.5, 7.7)
neither:
3.4 (0.8, 14.5)
Hip
systemic + cement: 1
systemic only:
1.8 (1.1, 3.0)
cement only:
2.7 (0.8, 8.7)
neither:
4.9 (1.2, 20.2)
*Jamsen adjusted for age, gender, diagnosis, type of implanted prosthesis;
Engesaeter adjusted for age, sex, cement and prosthesis brand, type of operating theatre,
operating time
200
v0.1 03.25.10
FUTURE RESEARCH
While many of the recommendations in this guideline are supported by high quality
evidence, certain areas are still lacking in high quality evidence. A number of diagnostic
tests exist and no single test has yet been identified that consistently allows the clinician
to rule in or rule out the presence of a periprosthetic infection in all patients. Given the
potential problems with instituting treatment and missing this diagnosis, future research
in the area of diagnosing a periprosthetic joint infection is warranted.
Specifically, further studies that characterize facets of the patient’s history and physical
examination as well as the presence of comorbidities that may affect the probability of a
periprosthetic joint infection are needed to help guide diagnostic algorithms.
Molecular techniques to aid in the diagnosis of PJI are currently under investigation. This
includes the use of microarrays, the polymerase chain reaction (PCR), proteomics, and
ELISA for measuring various cytokines, enzymes, IL-6, and neutrophil enzymes.The
routine role of sonification of removed implants and cement spacers also needs to be
clarified. At the time of publication of these guidelines, there are inconclusive results to
recommend the use or cost-effectiveness of these tests in clinical practice. Thus, further
studies are needed to determine their utility.
While there was strong evidence to support the use of an erythrocyte sedimentation rate
and c-reactive protein as initial screening tests for infection, the value of these tests for
patients with inflammatory arthritis (such as rheumatoid arthritis) or other systemic
diseases associated with increased ESR and CRP levels is unclear.
There is currently inadequate evidence to support or refute the role of wound swab in
management of patients with suspected periprosthetic joint infection. The efficacy of
various tests at the second stage of a two-stage operation for known periprosthetic
infection also requires clarification.
Patients who present with a painful total hip or total knee arthroplasty, who do not
otherwise have a clear indication for reoperation or revision, also present a diagnostic
challenge as cultures from the joint may be difficult or impossible to obtain. Further,
analysis of the value of non-invasive testing modalities, that do not rely on direct
sampling from around the prosthesis (such as advance imaging studies) would be of
value.
Finally, the effect that antibiotic treatment has on the utility of many of the commonly
used tests for diagnosing a periprosthetic joint infection is incompletely understood.
Many patients suspected of a periprosthetic joint infection may have received prior
treatment with antibiotics and the temporal effect of such treatment is unclear. While the
work group issued a strong recommendation against the administration of antibiotics
prior to obtaining a culture from the joint, many patients unfortunately have had such
treatment by the time they are evaluated by an Orthopaedic surgeon adding to the
diagnostic challenge. Finally, while the benefits of prophylactic antibiotics prior to the
surgical incision for preventing surgical site infections is clear, the benefit of withholding
such antibiotic prophylaxis prior to obtaining deep cultures at the time of re-operation or
201
v0.1 03.25.10
revision is unclear, and future studies that examine the effect of a single prophylactic
dose of antibiotics on the sensitivity of operative cultures are warranted.
202
v0.1 03.25.10
V. APPENDIXES
203
v0.1 03.25.10
APPENDIX I
WORK GROUP
Craig Della Valle MD, Chair
1611 W Harrison St # 300
Chicago, IL 60612-4861
Guidelines and Technology Oversight
Chair:
William C. Watters III MD
6624 Fannin #2600
Houston, TX 77030
Javad Parvizi, MD, Vice-Chair
Rothman Institute
925 Chestnut St - 5th Fl
Philadelphia, PA 19107
Evidence Based Practice Committee Chair:
Michael Keith, MD
2500 Metro Health Drive
Cleveland, OH 44109-1900
Thomas W Bauer, MD PhD
Cleveland Clinic Foundation
Department of Pathology
9500 Euclid Ave Desk L25
Cleveland, OH 44195
AAOS Staff:
Charles M. Turkelson, PhD
Director of Research and Scientific Affairs
6300 N River Road
Rosemont, IL 60018
Paul E DiCesare, MD
UC Davis Medical Center
Department of Orthopaedic Surgery
4860 Y St Ste 3800
Sacramento, CA 95817
Janet L. Wies MPH
AAOS Clinical Practice Guideline Mgr
Patrick Sluka MPH
AAOS Lead Research Analyst
Richard Parker Evans, MD
University of Arkansas for Medical Sciences
Department of Orthopedics
4301 W Markham, #531
Little Rock, AR 72205
Kristin Hitchcock
AAOS Medical Librarian
Special Acknowledgements
Sara Anderson MPH
Kevin Boyer
Laura Raymond, MA
John Segreti, MD
600 S Paulina St. Ste 143
Chicago, Il 60612
Mark Spangehl, MD
Mayo Clinic
5777 East Mayo Blvd
Phoenix, AZ 85054
204
v0.1 03.25.10
APPENDIX II
AAOS BODIES THAT APPROVED THIS CLINICAL PRACTICE GUIDELINE
Guidelines and Technology Oversight Committee
The AAOS Guidelines and Technology Oversight Committee (GTOC) consists of sixteen
AAOS members. The overall purpose of this Committee is to oversee the development of
the clinical practice guidelines, performance measures, health technology assessments
and utilization guidelines.
Evidence Based Practice Committee
The AAOS Evidence Based Practice Committee (EBPC) consists of ten AAOS members.
This Committee provides review, planning and oversight for all activities related to
quality improvement in orthopaedic practice, including, but not limited to evidence-based
guidelines, performance measures, and outcomes.
Council on Research, Quality Assessment, and Technology
To enhance the mission of the AAOS, the Council on Research, Quality Assessment, and
Technology promotes the most ethically and scientifically sound basic, clinical, and
translational research possible to ensure the future care for patients with musculoskeletal
disorders. The Council also serves as the primary resource to educate its members, the
public, and public policy makers regarding evidenced-based medical practice,
orthopaedic devices and biologics, regulatory pathways and standards development,
patient safety, occupational health, technology assessment, and other related areas of
importance.
The Council is comprised of the chairs of the AAOS Biological Implants, Biomedical
Engineering, Evidence Based Practice, Guidelines and Technology Oversight,
Occupational Health and Workers’ Compensation, Patient Safety, Research
Development, and US Bone and Joint Decade committees. Also on the Council are the
AAOS second vice-president, representatives of the Diversity Advisory Board, the
Women's Health Issues Advisory Board, the Board of Specialty Societies (BOS), the
Board of Councilors (BOC), the Communications Cabinet, the Orthopaedic Research
Society (ORS), the Orthopedic Research and Education Foundation (OREF), and three
members at large.
Board of Directors
The 17 member AAOS Board of Directors manages the affairs of the AAOS, sets policy,
and determines and continually reassesses the Strategic Plan.
205
v0.1 03.25.10
DOCUMENTATION OF APPROVAL
AAOS Work group Draft Completed
November 25, 2009
Peer Review Completed
December 28, 2009
Public Commentary Completed
April 15, 2010
AAOS Guidelines and Technology Oversight Committee
April 24, 2010
AAOS Evidence Based Practice Committee
April 24, 2010
AAOS Council on Research Quality Assessment
May 17, 2010
and Technology
AAOS Board of Directors
June 18, 2010
206
v0.1 03.25.10
APPENDIX III
STUDY ATTRITION FLOWCHART
6873 abstracts screened
for inclusion
6414 abstracts excluded
459 articles recalled for
full text review
105 articles recalled from
bibliography screening
473 articles excluded
91 articles included
207
v0.1 03.25.10
APPENDIX IV
LITERATURE SEARCHES
Search Strategy for PubMed
(periprosthetic[tiab] OR "Arthroplasty, Replacement, Hip"[Mesh] OR "Arthroplasty,
Replacement, Knee"[Mesh] OR "Hip Prosthesis"[mh] OR "Knee Prosthesis"[mh]
OR ((hip[tiab] OR "Hip Joint"[mh] OR knee[tiab] OR "Knee Joint"[mh] OR
acetabular[tiab] OR femoral[tiab] OR tibial[tiab] OR patellar[tiab])
AND (arthroplasty[tiab] OR implant[tiab] OR implants[tiab] OR "total joint"[tiab] OR
unicompartment*[tiab] OR replacement[tw] OR resurfacing[tiab] OR
hemiarthroplasty[tiab] OR component[tiab] OR (cup[tiab] AND stem[tiab]) OR
revision[tiab] OR resection[tiab] OR prosthesis[tiab] OR prostheses[tiab] OR
prosthetic[tiab] OR "Joint Prosthesis"[mh] OR "Prosthesis Failure"[mh]))) AND
(("Prosthesis-Related Infections"[mh] OR infection[tiab] OR infected[tiab] OR
"Sepsis"[mh] OR sepsis[tiab] OR septic[tiab] OR "Bacterial Infections"[mh] OR
"Bacteria"[mh] OR staphylococcus[tw] OR bacteria*[tiab] OR mycobacteria*[tw] OR
fungal[tw] OR fungus[tw] OR "Mycoses"[mh] OR coagulase negative staph[tw] OR
streptococcus[tw] OR acid-fast bacillus[tw] OR afb[tiab] OR gram positive[tw] OR gram
negative[tw] OR staphylococcus epidermidis[tw] OR pus[tw] OR
"Suppuration"[mh:noexp] OR purulence[tw]) OR ((pain[tiab] OR painful[tiab] OR
"Pain"[mh:noexp] OR stiffness[tw] OR warmth[tw] OR effusion[tw] OR redness[tw] OR
swelling[tw] OR bacteremia[tw] OR candidemia[tw]) AND ("Postoperative
Complications/radiography"[mh] OR "Postoperative Complications/pathology"[mh]OR
x-ray[tiab] OR "Blood Cell Count"[mh] OR cbc[tw] OR "Blood Sedimentation"[mh] OR
sedimentation rate[tw] OR "Erythrocyte Aggregation"[mh] OR "C-Reactive Protein"[mh]
OR "c-reactive protein"[tw] OR serology[tw] OR "Biopsy, Needle"[mh] OR
aspiration[tiab] OR "frozen section*"[tw] OR histology[tw] OR "Diagnostic
Imaging"[mh] OR "Radiopharmaceuticals/diagnostic use"[mh] OR sulfur colloid[tw] OR
gallium[tw] OR indium-111[tw] OR fdg-pet[tw] OR technetium-99[tw] OR MRI[tw] OR
(ct[tiab] AND scan[tiab])))) AND English[lang] AND 1970:2009/08/10[dp] NOT
(comment[pt] OR editorial[pt] OR letter[pt] OR addresses[pt] OR news[pt] OR
"newspaper article"[pt] OR "case reports"[pt] OR "historical article"[pt])
Sorted by study type
#1 Systematic[sb]
#2 (randomized controlled trial[pt] OR controlled clinical trial[pt] OR "randomized
controlled trials as topic"[mh] OR random allocation[mh] OR double-blind method[mh]
OR single-blind method[mh] OR clinical trial[pt] OR "clinical trials as topic"[mh] OR
"clinical trial"[tw] OR ((singl*[tw] OR doubl*[tw] OR trebl*[tw] OR tripl*[tw]) AND
(mask*[tw] OR blind*[tw])) OR "latin square"[tw] OR placebos[mh] OR placebo*[tw]
OR random*[tw] OR research design[mh:noexp] OR "comparative study "[pt] OR
"evaluation studies as topic"[mh] OR "evaluation studies "[pt] OR "follow-Up
208
v0.1 03.25.10
studies"[mh] OR "prospective studies"[mh] OR "cross-over studies"[mh] OR
control*[tw] OR prospectiv*[tw] OR volunteer*[tw])
NOT #1 OR #2
Search strategy for EMBASE
(‘hip arthroplasty’/de OR ‘total hip prosthesis’/de OR ‘acetabuloplasty’/de OR ‘knee
arthroplasty’/de OR ‘total knee replacement’/de) AND
((‘infection’/de OR ‘gram negative infection’/de OR ‘gram negative sepsis’/de OR
‘staphylococcus infection’/de OR ‘streptococcus infection’/de OR ‘mycosis’/exp OR
‘infection control’/de OR ‘infection rate’/de OR ‘infection prevention’/de OR ‘infection
risk’/de OR ‘bacterial infection’/exp OR ‘postoperative infection’/de OR ‘prosthesis
infection’/de)
OR ((pain OR painful OR stiffness OR warmth OR effusion OR redness OR swelling OR
bacteremia/de OR candidemia/de) AND (‘hip radiography’/de OR ‘knee radiography’/de
OR ‘frozen section’/de OR ‘blood cell count’/de OR ‘erythrocyte sedimentation rate’/de
OR ‘c reactive protein’/de OR ‘aspiration biopsy’/de OR ‘joint aspiration’/de OR
‘nuclear magnetic resonance’/exp OR ‘computer assisted tomography’/exp OR
‘diagnostic imaging’/de OR ‘radiopharmaceutical agent’/exp)))
AND ([article]/lim OR [conference paper]/lim OR [review]/lim) AND [english]/lim
AND [embase]/lim
#1 'meta analysis' OR 'systematic review' OR medline
#2 random* OR 'clinical trial' OR 'health care quality'/exp
NOT #1 OR #2
Search strategy for CINAHL
((MM “Arthroplasty, Replacement, Hip” or MM “Arthroplasty, Replacement, Knee” or
((hip or knee) and (replacement* or prosthesis or prostheses or implant*))) AND
(infection or infected or MM infection+ or MM mycoses+ or MM “Prosthesis-Related
Infections” or MM “Bacterial Infections+” or MM Streptococcus+ or MM
Staphylococcus+ or MM “Staphylococcal Infections” or MM “Streptococcal Infections+”
or MM Sepsis+ or MM Suppuration))
and PT “research” and LA English and PY 1970-2009
NOT
PT “editorial” or PT “letter” or PT “case study” or MM “case studies”
209
v0.1 03.25.10
#1 (MM “meta analysis” or MM “systematic review” or PT “systematic review”)
NOT (#1)
Search strategy for Cochrane Central
(joint):ti,ab,kw and (arthroplasty OR prosthesis OR prosthetic OR replacement OR
implant):ti,ab,kw and (hip OR knee OR acetabular):ti,ab,kw and (infection OR
infected):ti,ab,kw
210
v0.1 03.25.10
APPENDIX V
DATA EXTRACTION ELEMENTS
The data elements below were extracted into electronic forms in Microsoft® Excel. The
extracted information includes:
Study Characteristics
• Selection criteria
• Reference standard details
• Index test details
• Blinding of index test results when interpreting reference standard
• Blinding of reference standard results when interpreting index test
• Withdrawals from study
Results
•
•
•
•
•
True positives
True negatives
False positives
False negatives
Uninterpretable/intermediate results
211
v0.1 03.25.10
APPENDIX VI
JUDGING THE QUALITY OF DIAGNOSTIC STUDIES
The QUADAS tool108-110 is used to identify sources of bias, variability, and the quality of
reporting in studies of diagnostic accuracy. Fourteen questions answered “yes”, “no”, or
“unclear” contribute to the QUADAS tool. There is no score derived from the use of the
QUADAS tool.
Was the spectrum of patient’s representative of the patients who will receive the test in
practice?
Were selection criteria clearly described?
Is the reference standard likely to correctly classify the target condition?
Is the time period between ref. standard and index test short enough to be reasonably sure
that the target condition did not change between the two tests?
Did the whole sample or a random selection of the sample, receive verification using a
reference standard of diagnosis?
Did patients receive the same reference standard regardless of the index test result?
Was the reference standard independent of the index test (i.e. the index test did not form
part of the reference standard)?
Was the execution of the index test described in sufficient detail to permit replication of
the test?
Was the execution of the reference standard described in sufficient detail to permit its
replication?
Were the index test results interpreted without knowledge of the results of the reference
standard?
Were the reference standard results interpreted without knowledge of the results of the
index test?
Were the same clinical data available when test results were interpreted as would be
available when the test is used in practice?
Were uninterpretable/intermediate test results reported?
Were withdrawals from the study explained?
212
v0.1 03.25.10
JUDGING THE QUALITY OF PROGNOSTIC STUDIES
Were the variables of interest clearly identified in the Methods section?
Were all variables of interest discussed in the Results section?
Were there sufficient patients per variable?
Were there sufficient events per variable?
If coding of variables is used, is the coding scheme described or unambiguous?
Collinearity has been tested or there is no obvious potential for collinearity?
Was the fitting procedure explicitly stated?
Were any goodness-of-fit statistics reported?
Was the model subjected to a test of validation?
JUDGING THE QUALITY OF TREATMENT STUDIES
RANDOMIZED CONTROLLED TRIALS
Did the study employ stochastic randomization?
Was there concealment of allocation?
Were subjects blinded to the treatment they received?
Were those who assessed/rated the patient’s outcomes blinded to the group to which the
patients were assigned?
Was there more than 80% follow-up for all patients in the control group and the
experimental group on the outcome of interest?
Did patients in the different study groups have similar levels of performance on ALL of
the outcome variables at the time they were assigned to groups?
For randomized crossover studies, was there evidence that the results obtained in the
study’s two experimental groups (in period 1 and 2) did not differ?
For randomized crossover studies, was there evidence that the results of the two control
groups (in period 1 and 2) did not differ?
213
v0.1 03.25.10
APPENDIX VII
FORM FOR ASSIGNING STRENGTH OF RECOMMENDATION
(INTERVENTIONS)
GUIDELINE RECOMMENDATION___________________________________
PRELIMINARY STRENGTH OF RECOMMENDATION: ________________
STEP 1:
LIST BENEFITS AND HARMS
Please list the benefits (as demonstrated by the systematic review) of the intervention.
Please list the harms (as demonstrated by the systematic review) of the intervention.
Please list the benefits for which the systematic review is not definitive.
Please list the harms for which the systematic review is not definitive.
STEP 2:
IDENTIFY CRITICAL OUTCOMES
Please circle the above outcomes that are critical for determining whether the intervention
is beneficial and whether it is harmful.
Are data about critical outcomes lacking to such a degree that you would lower the
preliminary strength of the recommendation?
What is the resulting strength of recommendation?
STEP 3:
EVALUATE APPLICABILITY OF THE EVIDENCE
Is the applicability of the evidence for any of the critical outcomes so low that
substantially worse results are likely to be obtained in actual clinical practice?
Please list the critical outcomes backed by evidence of doubtful applicability.
Should the strength of recommendation be lowered because of low applicability?
STEP 4:
BALANCE BENEFITS AND HARMS
Are there trade-offs between benefits and harms that alter the strength of
recommendation obtained in STEP 3?
214
v0.1 03.25.10
STEP 5
CONSIDER STRENGTH OF EVIDENCE
Does the strength of the existing evidence alter the strength of recommendation obtained
in STEP 4?
NOTE: Because we are not performing a formal cost analyses, you should only consider
costs if their impact is substantial.
215
v0.1 03.25.10
APPENDIX VIII
VOTING BY THE NOMINAL GROUP TECHNIQUE
Voting on guideline recommendations will be conducted using a modification of the
nominal group technique (NGT), a method previously used in guideline development.71
Briefly each member of the guideline workgroup ranks his or her agreement with a
guideline recommendation on a scale ranging from 1 to 9 (where 1 is “extremely
inappropriate” and 9 is “extremely appropriate”). Consensus is obtained if the number of
individuals who do not rate a measure as 7, 8, or 9 is statistically non-significant (as
determined using the binomial distribution). Because the number of workgroup members
who are allowed to dissent with the recommendation depends on statistical significance,
the number of permissible dissenters varies with the size of the workgroup. The number
of permissible dissenters for several workgroup sizes is given in the table below:
Workgroup Size
≤3
Number of Permissible
Dissenters
Not allowed, statistical
significance cannot be
obtained
4-5
0
6-8
1
9
1 or 2
The NGT is conducted by first having members vote on a given recommendation without
discussion. If the number of dissenters is “permissible”, the recommendation is adopted
without further discussion. If the number of dissenters is not permissible, there is further
discussion to see whether the disagreement(s) can be resolved. Three rounds of voting are
held to attempt to resolve disagreements. If disagreements are not resolved after three
voting rounds, no recommendation is adopted.
OPINION-BASED RECOMMENDATIONS
A guideline can contain recommendations that are backed by little or no data. Under such
circumstances, work groups often issue opinion-based recommendations. Although doing
so is sometimes acceptable in an evidence-based guideline (expert opinion is a form of
evidence), it is also important to avoid constructing a guideline that liberally uses expert
opinion; research shows that expert opinion is often incorrect.
Opinion-based recommendations are developed only if they address a vitally important
aspect of patient care. For example, constructing an opinion-based recommendation in
favor of taking a history and physical is warranted. Constructing an opinion-based
recommendation in favor of a specific modification of a surgical technique is seldom
warranted. To ensure that an opinion-based recommendation is absolutely necessary, the
216
v0.1 03.25.10
AAOS has adopted rules to guide the content of the rationales that underpin such
recommendations. These rules are based on those outlined by the US Preventive Services
Task Force (USPSTF).81 Specifically, rationales based on expert opinion must:
•
Not contain references to or citations from articles not included in the
systematic review that underpins the recommendation.
•
Not contain the AAOS guideline language “We Recommend”, “We suggest”
or “treatment x is an option”.
•
Contain an explanation of the potential preventable burden of disease. This
involves considering both the incidence and/or prevalence of the disease,
disorder, or condition and considering the associated burden of suffering. To
paraphrase the USPSTF, when evidence is insufficient, provision of a
treatment (or diagnostic) for a serious condition might be viewed more
favorably than provision of a treatment (or diagnostic) for a condition that
does not cause as much suffering. The AAOS (like the USPSTF) understand
that evaluating the “burden of suffering” is subjective and involves judgment.
This evaluation should be informed by patient values and concerns. The
considerations outlined in this bullet make it difficult to recommend new
technologies. It is not appropriate for a guideline to recommend widespread
use of a technology backed by little data and for which there is limited
experience. Such technologies are addressed in the AAOS’ Technology
Overviews.
•
Address potential harms. In general, “When the evidence is insufficient, an
intervention with a large potential for harm (such as major surgery) might be
viewed less favorably than an intervention with a small potential for harm
(such as advice to watch less television).”81
•
Address apparent discrepancies in the logic of different recommendations.
Accordingly, if there are no relevant data for several recommendations and the
work group chooses to issue an opinion-based recommendation in some cases
but chooses not to make a recommendation in other cases, the rationales for
the opinion-based recommendations must explain why this difference exists.
Information garnered from the previous bullet points will be helpful in this
regard.
•
Consider current practice. The USPSTF specifically states that clinicians
justifiably fear that not doing something that is done on a widespread basis
will lead to litigation.81The consequences of not providing a service that is
neither widely available nor widely used are less serious than the
consequences of not providing a treatment accepted by the medical profession
and thus expected by patients. Discussions of available treatments and
procedures rely on mutual communication between the patient’s guardian and
physician, and on weighing the potential risks and benefits for a given patient.
The patient’s “expectation of treatment” must be tempered by the treating
217
v0.1 03.25.10
physician’s guidance about the reasonable outcomes that the patient can
expect.
•
Justify, why a more costly device, drug, or procedure is being recommended
over a less costly one whenever such an opinion-based recommendation is
made.
Work group members write the rationales for opinion based recommendations on the first
day of the final work group meeting. When the work group re-convenes on the second
day of its meeting, it will vote on the rationales. The typical voting rules will apply. If the
work group cannot adopt a rationale after three votes, the rationale and the opinion-based
recommendation will be withdrawn, and a “recommendation” stating that the group can
neither recommend for or against the recommendation in question will appear in the
guideline.
Discussions of opinion-based rationales may cause some members to change their minds
about whether to issue an opinion-based recommendation. Accordingly, at any time
during the discussion of the rationale for an opinion-based recommendation, any member
of the work group can make a motion to withdraw that recommendation and have the
guideline state that the work group can neither recommend for or against the
recommendation in question.
CHECKLIST FOR VOTING ON OPINION-BASED RECOMMENDATIONS
When voting on the rationale, please consider the following:
1. Does the recommendation affect a substantial number of patients or address
treatment (or diagnosis) of a condition that causes death and/or considerable
suffering?
2. Does the recommendation address the potential harms that will be incurred if it is
implemented and, if these harms are serious, does the recommendation justify;
a. why the potential benefits outweigh the potential harms and/or
b. why an alternative course of treatment (or diagnostic workup) that
involves less serious or fewer harms is not being recommended?
3. Does the rationale explain why the work group chose to make a recommendation
in the face of minimal evidence while, in other instances, it chose to make no
recommendation in the face of a similar amount of evidence?
4. Does the rationale explain that the recommendation is consistent with current
practice?
5. If relevant, does the rationale justify why a more costly device, drug, or procedure
is being recommended over a less costly one?
218
v0.1 03.25.10
APPENDIX IX
STRUCTURED PEER REVIEW FORM
Review of any AAOS confidential draft allows us to improve the overall guideline
but does not imply endorsement by any given individual or any specialty society
who participates in our review processes. The AAOS review process may result in
changes to the documents; therefore, endorsement cannot be solicited until the
AAOS Board of Directors officially approves the final guideline.
Reviewer Information:
Name of Reviewer_________________________________________
Address_________________________________________________
City___________________ State_________________ Zip Code___________
Phone _____________________Fax ________________________
E-mail_______________________
Specialty Area/Discipline: _______________________________________
Work setting: _________________________________________________
Credentials: _________________________________________________
May we list you as a Peer Reviewer in the final Guidelines?
Yes
No
Are you reviewing this guideline as
a representative of a professional society?
Yes
No
If yes, may we list your society as a reviewer
of this guideline?
Yes
No
Reviewer Instructions
Please read and review this Draft Clinical Practice Guideline and its associated Evidence
Report with particular focus on your area of expertise. Your responses are confidential
and will be used only to assess the validity, clarity, and accuracy of the interpretation of
the evidence. If applicable, please specify the draft page and line numbers in your
comments. Please feel free to also comment on the overall structure and content of the
guideline and Evidence Report.
If you need more space than is provided, please attach additional pages.
Please complete and return this form electronically to [email protected] or fax the form
back to Jan Wies at (847) 823-9769.
Thank you in advance for your time in completing this form and giving us your feedback.
We value your input and greatly appreciate your efforts. Please send the completed form
and comments by Month/Day/Year.
219
v0.1 03.25.10
220
v0.1 03.25.10
COMMENTS
Please provide a brief explanation of both your positive and negative answers in the
preceding section. If applicable, please specify the draft page and line numbers in your
comments. Please feel free to also comment on the overall structure and content of the
guideline and Evidence Report
OVERALL ASSESSMENT
Would you recommend these guidelines for use in practice? (check one)
Strongly recommend
_______
Recommend (with provisions or alterations)
_______
Would not recommend
_______
Unsure
_______
COMMENTS:
Please provide the reason(s) for your recommendation.
221
v0.1 03.25.10
APPENDIX X
PEER REVIEW PANEL
Peer review of the draft guideline is completed by an outside Peer Review Panel. Outside
peer reviewers are solicited for each AAOS guideline and consist of experts in the
guideline’s topic area. These experts represent professional societies other than AAOS
and are nominated by the guideline workgroup prior to beginning work on the guideline.
For this guideline, 14 outside peer review organizations were invited to review the draft
guideline and all supporting documentation. Eight of these societies participated in the
review of the guideline draft and five explicitly consented to be listed as a peer review
organization in this appendix.
The organizations that reviewed the document and consented to be listed as a peer
review organization are listed below:
American Association of Hip and Knee Surgeons
European Bone and Joint Infection Society
Knee Society
Musculoskeletal Infection Society
Society of Nuclear Medicine
Individuals who participated in the peer review of this document and gave their
consent to be listed as reviewers of this document are:
Thomas K. Fehring MD
Kevin L. Garvin MD
Arlen D. Hanssen MD
James I. Huddleston MD
Douglas R. Osmon MD
Christopher J. Palestro MD
Geert H.I.M. Walenkamp MD, PhD.
Barbara Weissman MD
The Society for Nuclear Medicine Standards Committee
222
v0.1 03.25.10
PUBLIC COMMENTARY
A period of public commentary follows the peer review of the draft guideline. If
significant non-editorial changes are made to the document as a result of public
commentary, these changes are also documented and forwarded to the AAOS bodies that
approve the final guideline.
Public commentators who gave explicit consent to be listed in this document include the
following:
William Jiranek MD
Andrew H. Schmidt MD, Orthopaedic Trauma Association
Participation in the AAOS guideline public commentary review process does not
constitute an endorsement of the guideline by the participating organizations or the
individual listed nor does it is any way imply the reviewer supports this document.
223
v0.1 03.25.10
APPENDIX XI
INTERPRETING THE FOREST PLOTS
Throughout the guideline we use descriptive diagrams or forest plots to present data from
studies comparing a diagnostic test to a reference standard. In the example below, the
positive and negative likelihood ratios are the effect measures used to depict study
results. The horizontal line running through each point represents the 95% confidence
interval for that point. In this graph, the solid vertical line represents “no effect” where
the likelihood ratio is equal to one. The dashed line represents the value of a likelihood
ratio that indicates a large and conclusive change in the probability of disease.
For example, in the figure below the summary estimate (diamond) indicates a positive
likelihood ratio close to 10 and a negative likelihood ratio of between 0.2 and 0.5. This
result is statistically significant because the 95% Confidence Interval does not cross the
“no effect” line. Please note that summary measures are not reported in the plot if high
heterogeneity (>50%) was present.
StudyId
StudyId
Glithero
Glithero
Della Valle
Della Valle
Fink
Fink
Barrack
Barrack
Malhotra
Malhotra
Eisler
Eisler
Mulcahy
Mulcahy
Williams
Williams
Lachiewicz
Lachiewicz
COMBINED
COMBINED
1
2
5 10
.1 .2
.5
1
DLR NEGATIVE
DLR POSITIVE
224
v0.1 03.25.10
APPENDIX XII
CONFLICT OF INTEREST
All members of the AAOS workgroup disclosed any conflicts of interest prior to the
development of the recommendations for this guideline. Conflicts of interest are
disclosed in writing with the American Academy of Orthopaedic Surgeons via a private
on-line reporting database and also verbally at the recommendation approval meeting.
Disclosure Items: (n) = Respondent answered 'No' to all items indicating no conflicts.
1=Board member/owner/officer/committee appointments; 2= Medical/Orthopaedic
Publications; 3= Royalties; 4= Speakers bureau/paid presentations;5A= Paid consultant;
5B= Unpaid consultant; 6= Research or institutional support from a publisher; 7=
Research or institutional support from a company or supplier; 8= Stock or Stock Options;
9= Other financial/material support from a publisher; 10= Other financial/material
support from a company or supplier.
Thomas W Bauer, MD, PhD: (Cleveland, OH): 2 (Journal of Bone and Joint Surgery American); 5A (Musculoskeletal Transplant Foundation; Osteotech; Smith & Nephew;
Stryker). Submitted on: 08/27/2008.
Craig J Della Valle, MD: 2 (Clinical Orthopaedics and Related Research; Journal of the
American Academy of Orthopedic Surgeons; SLACK Incorporated); 4 (Angiotech); 5A
(Zimmer); 5B (Biomet; Kinamed); 7 (Zimmer); 10 (Smith & Nephew; Stryker).
Submitted on: 08/17/2008.
Paul E DiCesare, MD: 5A (Stryker); 7 (Stryker). Submitted on: 08/11/2008.
Richard Parker Evans, MD: 1 (American Academy of Orthopedic Surgeons); 4
(DePuy, A Johnson & Johnson Company; Smith & Nephew; Cubist); 5A (DePuy, A
Johnson & Johnson Company; Smith & Nephew; Cubist); 5B (3M); 7 (National Institutes
of Health (NIAMS & NICHD); Biomet; Cubist). Submitted on: 12/07/2007 and last
confirmed as accurate on 04/17/2008.
Michael Warren Keith, MD: (n). Submitted on: 10/10/2007 at 08:42 AM and last
confirmed as accurate on 04/09/2008.
Javad Parvizi, MD: 1 (Smarttech LLC); 2 (Clinical Orthopaedics and Related Research;
Journal of Arthroplasty; Journal of Bone and Joint Surgery - American; Journal of Bone
and Joint Surgery - British; Journal of Orthopaedic Research; Journal of the American
Academy of Orthopedic Surgeons); 4 (Johnson & Johnson); 5A (Stryker; Smith &
Nephew); 7 (Stryker). Submitted on: 10/10/2007.
John Segreti, MD: (Chicago, IL): 4 (Johnson & Johnson; Merck; Pfizer; Wyeth; Cubist);
5A (Johnson & Johnson; Pfizer; Wyeth); 5B (Medtronic); 7 (Abbott; Bristol-Myers
Squibb; Health and Human Services; Merck; Cubist); 8 (Pfizer; Zimmer). Submitted on:
08/12/2008.
225
v0.1 03.25.10
Mark J Spangehl, MD (Phoenix, AZ): (n). Submitted on: 08/12/2008.
William Charles Watters III, MD: 1 (North American Spine Society; Work Loss Data
Institute); 2 (The Spine Journal); 5A (Stryker; Intrinsic Therapeutics; MeKessen Health
Care Solutions). Submitted on: 10/09/2007 at 08:09 PM and last confirmed as accurate on
04/23/2008.
226
v0.1 03.25.10
APPENDIX XIII
REFERENCES
Reference List
(1) Amin AK, Clayton RAE, Patton JT, Gaston M, Cook RE, Brenkel IJ. Total knee
replacement in morbidly obese patients: Results of a prospective, matched study.
Journal of Bone and Joint Surgery - Series B 2006;88(10):1321-1326.
(2) Atkins BL, Athanasou N, Deeks JJ et al. Prospective evaluation of criteria for
microbiological diagnosis of prosthetic-joint infection at revision arthroplasty.
The OSIRIS Collaborative Study Group. J Clin Microbiol 1998;36(10):29322939.
(3) Banit DM, Kaufer H, Hartford JM. Intraoperative frozen section analysis in
revision total joint arthroplasty. Clin Orthop Relat Res 2002;(401):230-238.
(4) Barrack RL, Harris WH. The value of aspiration of the hip joint before revision
total hip arthroplasty. J Bone Joint Surg Am 1993;75(1):66-76.
(5) Barrack RL, Jennings RW, Wolfe MW, Bertot AJ. The Coventry Award. The
value of preoperative aspiration before total knee revision. Clin Orthop Relat Res
1997;(345):8-16.
(6) Berbari EF, Hanssen AD, Duffy MC et al. Risk factors for prosthetic joint
infection: case-control study. Clin Infect Dis 1998;27(5):1247-1254.
(7) Bergqvist D, Gudmundsson G, Hallbook T. Does thromboprophylaxis increase
the risk for infectious complications after total hip replacement? Vasa - Journal of
Vascular Diseases 1985;14(3):269-271.
(8) Bernard L, Lubbeke A, Stern R et al. Value of preoperative investigations in
diagnosing prosthetic joint infection: retrospective cohort study and literature
review. Scand J Infect Dis 2004;36(6-7):410-416.
(9) Bernay I, Akinci M, Kitapci M, Tokgozoglu N, Erbengi G. The value of Tc-99m
Nanocolloid scintigraphy in the evaluation of infected total hip arthroplasties.
Annals of Nuclear Medicine 1993;7(4):215-222.
(10) Bordini B, Stea S, Cremonini S, Viceconti M, De PR, Toni A. Relationship
between obesity and early failure of total knee prostheses. BMC Musculoskelet
Disord 2009;10:29.
(11) Bottner F, Wegner A, Winkelmann W, Becker K, Erren M, Gotze C. Interleukin6, procalcitonin and TNF-alpha: markers of peri-prosthetic infection following
total joint replacement. J Bone Joint Surg Br 2007;89(1):94-99.
227
v0.1 03.25.10
(12) Bozic KJ, Kurtz SM, Lau E et al. The Epidemiology of Revision Total Knee
Arthroplasty in the United States. Clin Orthop Relat Res 2009.
(13) Bozic KJ, Kurtz SM, Lau E, Ong K, Vail TP, Berry DJ. The epidemiology of
revision total hip arthroplasty in the United States. J Bone Joint Surg Am
2009;91(1):128-133.
(14) Carlsson AK, Lidgren L, Lindberg L. Prophylactic antibiotics against early and
late deep infections after total hip replacements. Acta Orthop Scand
1977;48(4):405-410.
(15) Chryssikos T, Parvizi J, Ghanem E, Newberg A, Zhuang H, Alavi A. FDG-PET
imaging can diagnose periprosthetic infection of the hip. Clin Orthop Relat Res
2008;466(6):1338-1342.
(16) Confalonieri N, Manzotti A, Pullen C. Is closed-suction drain necessary in
unicompartmental knee replacement? A prospective randomised study. Knee
2004;11(5):399-402.
(17) Cook D.J., Mulrow CD, Haynes RB. Systematic Reviews:synthesis of best
evidence for clinical decisions. Ann Intern Med 1997;126(5):376-380.
(18) Crevoisier XM, Reber P, Noesberger B. Is suction drainage necessary after total
joint arthroplasty? A prospective study. Arch Orthop Trauma Surg
1998;117(3):121-124.
(19) Cyteval C, Hamm V, Sarrabere MP, Lopez FM, Maury P, Taourel P. Painful
infection at the site of hip prosthesis: CT imaging. Radiology 2002;224(2):477483.
(20) Delank KS, Schmidt M, Michael JW, Dietlein M, Schicha H, Eysel P. The
implications of 18F-FDG PET for the diagnosis of endoprosthetic loosening and
infection in hip and knee arthroplasty: results from a prospective, blinded study.
BMC Musculoskelet Disord 2006;7:20.
(21) Della Valle CJ, Sporer SM, Jacobs JJ, Berger RA, Rosenberg AG, Paprosky WG.
Preoperative testing for sepsis before revision total knee arthroplasty. J
Arthroplasty 2007;22(6 Suppl 2):90-93.
(22) Della Valle CJ, Zuckerman JD, Di Cesare PE. Periprosthetic sepsis. Clin Orthop
Relat Res 2004;(420):26-31.
(23) Di Cesare PE, Chang E, Preston CF, Liu CJ. Serum interleukin-6 as a marker of
periprosthetic infection following total hip and knee arthroplasty. J Bone Joint
Surg Am 2005;87(9):1921-1927.
(24) Dowsey MM, Choong PF. Obesity is a major risk factor for prosthetic infection
after primary hip arthroplasty. Clin Orthop Relat Res 2008;466(1):153-158.
228
v0.1 03.25.10
(25) Dowsey MM, Choong PF. Obese Diabetic Patients are at Substantial Risk for
Deep Infection after Primary TKA. CLIN ORTHOP RELATED RES
2009;467(6):1577-1581.
(26) Doyon F, Evrard J, Mazas F, Hill C. Long-term results of prophylactic cefazolin
versus placebo in total hip replacement. Lancet 1987;1(8537):860.
(27) Eisler T, Svensson O, Engstrom CF et al. Ultrasound for diagnosis of infection in
revision total hip arthroplasty. J Arthroplasty 2001;16(8):1010-1017.
(28) Engesaeter LB, Lie SA, Espehaug B, Furnes O, Vollset SE, Havelin LI. Antibiotic
prophylaxis in total hip arthroplasty: effects of antibiotic prophylaxis systemically
and in bone cement on the revision rate of 22,170 primary hip replacements
followed 0-14 years in the Norwegian Arthroplasty Register. Acta Orthop Scand
2003;74(6):644-651.
(29) Esler CN, Blakeway C, Fiddian NJ. The use of a closed-suction drain in total knee
arthroplasty. A prospective, randomised study. J Bone Joint Surg Br
2003;85(2):215-217.
(30) Fehring TK, McAlister JA, Jr. Frozen histologic section as a guide to sepsis in
revision joint arthroplasty. Clin Orthop Relat Res 1994;(304):229-237.
(31) Fink B, Makowiak C, Fuerst M, Berger I, Schafer P, Frommelt L. The value of
synovial biopsy, joint aspiration and C-reactive protein in the diagnosis of late
peri-prosthetic infection of total knee replacements. J Bone Joint Surg Br
2008;90(7):874-878.
(32) Frances BA, Martinez FM, Cebrian Parra JL, Graneda DS, Crespo RG, LopezDuran SL. Diagnosis of infection in hip and knee revision surgery: intraoperative
frozen section analysis. Int Orthop 2007;31(1):33-37.
(33) Ghanem E, Parvizi J, Burnett RS et al. Cell count and differential of aspirated
fluid in the diagnosis of infection at the site of total knee arthroplasty. J Bone
Joint Surg Am 2008;90(8):1637-1643.
(34) Ghanem E, Parvizi J, Clohisy J, Burnett S, Sharkey PF, Barrack R. Perioperative
antibiotics should not be withheld in proven cases of periprosthetic infection. Clin
Orthop Relat Res 2007;461:44-47.
(35) Glithero PR, Grigoris P, Harding LK, Hesslewood SR, McMinn DJ. White cell
scans and infected joint replacements. Failure to detect chronic infection. J Bone
Joint Surg Br 1993;75(3):371-374.
(36) González D, V, Slullitel G, Vestri R, Comba F, Buttaro M, Piccaluga F. No need
for routine closed suction drainage in elective arthroplasty of the hip: a
prospective randomized trial in 104 operations. Acta orthopaedica Scandinavica
2004;75:30-33.
229
v0.1 03.25.10
(37) Greidanus NV, Masri BA, Garbuz DS et al. Use of erythrocyte sedimentation rate
and C-reactive protein level to diagnose infection before revision total knee
arthroplasty. A prospective evaluation. J Bone Joint Surg Am 2007;89(7):14091416.
(38) Harbord RM, Deeks JJ, Egger M, Whiting P, Sterne JA. A unification of models
for meta-analysis of diagnostic accuracy studies. Biostatistics 2007;8(2):239-251.
(39) Harbord RM, Whiting P, Sterne JA et al. An empirical comparison of methods for
meta-analysis of diagnostic accuracy showed hierarchical models are necessary. J
Clin Epidemiol 2008;61(11):1095-1103.
(40) Holt BT, Parks NL, Engh GA, Lawrence JM. Comparison of closed-suction
drainage and no drainage after primary total knee arthroplasty. Orthopedics
1997;20(12):1121-1124.
(41) Huotari K, Lyytikainen O, Seitsalo S. Patient outcomes after simultaneous
bilateral total hip and knee joint replacements. J Hosp Infect 2007;65(3):219-225.
(42) Jaeschke R, Guyatt G, Lijmer J. Diagnostic Tests. In: Guyatt G, Drummond R,
editors. Users' Guides to the Medical Literature: A Manual for Evidence-Based
Clinical Practice.Chicago: AMA; 2007. 121-140.
(43) Jamsen E, Huhtala H, Puolakka T, Moilanen T. Risk factors for infection after
knee arthroplasty. A register-based analysis of 43,149 cases. J Bone Joint Surg
Am 2009;91(1):38-47.
(44) Jenny JY, Boeri C, Lafare S. No drainage does not increase complication risk
after total knee prosthesis implantation: a prospective, comparative, randomized
study. Knee Surg Sports Traumatol Arthrosc 2001;9(5):299-301.
(45) Johansson T, Engquist M, Pettersson LG, Lisander B. Blood loss after total hip
replacement: a prospective randomized study between wound compression and
drainage. J Arthroplasty 2005;20(8):967-971.
(46) Johnson JA, Christie MJ, Sandler MP, Parks PF, Jr., Homra L, Kaye JJ. Detection
of occult infection following total joint arthroplasty using sequential technetium99m HDP bone scintigraphy and indium-111 WBC imaging. J Nucl Med
1988;29(8):1347-1353.
(47) Joseph TN, Mujtaba M, Chen AL et al. Efficacy of combined technetium-99m
sulfur colloid/indium-111 leukocyte scans to detect infected total hip and knee
arthroplasties. J Arthroplasty 2001;16(6):753-758.
(48) Kamme C, Lindberg L. Aerobic and anaerobic bacteria in deep infections after
total hip arthroplasty: differential diagnosis between infectious and non-infectious
loosening. Clin Orthop Relat Res 1981;(154):201-207.
230
v0.1 03.25.10
(49) Kersey R, Benjamin J, Marson B. White blood cell counts and differential in
synovial fluid of aseptically failed total knee arthroplasty. J Arthroplasty
2000;15(3):301-304.
(50) Khan LAK, Cowie JG, Ballantyne JA, Brenkel IJ. The complication rate and
medium-term functional outcome after total hip replacement in smokers. HIP
International 2009;19(1):47-51.
(51) Kim YH, Cho SH, Kim RS. Drainage versus nondrainage in simultaneous
bilateral total hip arthroplasties. J Arthroplasty 1998;13(2):156-161.
(52) Kim YH, Cho SH, Kim RS. Drainage versus nondrainage in simultaneous
bilateral total knee arthroplasties. Clin Orthop Relat Res 1998;(347):188-193.
(53) Klett R, Kordelle J, Stahl U et al. Immunoscintigraphy of septic loosening of knee
endoprosthesis: a retrospective evaluation of the antigranulocyte antibody BW
250/183. Eur J Nucl Med Mol Imaging 2003;30(11):1463-1466.
(54) Ko PS, Ip D, Chow KP, Cheung F, Lee OB, Lam JJ. The role of intraoperative
frozen section in decision making in revision hip and knee arthroplasties in a local
community hospital. J Arthroplasty 2005;20(2):189-195.
(55) Kraemer WJ, Saplys R, Waddell JP, Morton J. Bone scan, gallium scan, and hip
aspiration in the diagnosis of infected total hip arthroplasty. J Arthroplasty
1993;8(6):611-616.
(56) Kurtz SM, Ong KL, Lau E, Bozic KJ, Berry D, Parvizi J. Prosthetic joint infection
risk after TKA in the Medicare population. Clin Orthop Relat Res
2010;468(1):52-56.
(57) Lachiewicz PF, Rogers GD, Thomason HC. Aspiration of the hip joint before
revision total hip arthroplasty. Clinical and laboratory factors influencing
attainment of a positive culture. J Bone Joint Surg Am 1996;78(5):749-754.
(58) Levitsky KA, Hozack WJ, Balderston RA et al. Evaluation of the painful
prosthetic joint. Relative value of bone scan, sedimentation rate, and joint
aspiration. J Arthroplasty 1991;6(3):237-244.
(59) Lonner JH, Desai P, Dicesare PE, Steiner G, Zuckerman JD. The reliability of
analysis of intraoperative frozen sections for identifying active infection during
revision hip or knee arthroplasty. J Bone Joint Surg Am 1996;78(10):1553-1558.
(60) Love C, Marwin SE, Tomas MB et al. Diagnosing infection in the failed joint
replacement: a comparison of coincidence detection 18F-FDG and 111In-labeled
leukocyte/99mTc-sulfur colloid marrow imaging. J Nucl Med 2004;45(11):18641871.
231
v0.1 03.25.10
(61) Lubbeke A, Stern R, Garavaglia G, Zurcher L, Hoffmeyer P. Differences in
outcomes of obese women and men undergoing primary total hip arthroplasty.
Arthritis Rheum 2007;57(2):327-334.
(62) Luessenhop CP, Higgins LD, Brause BD, Ranawat CS. Multiple prosthetic
infections after total joint arthroplasty. Risk factor analysis. J Arthroplasty
1996;11(7):862-868.
(63) Magnuson JE, Brown ML, Hauser MF, Berquist TH, Fitzgerald RH, Jr., Klee GG.
In-111-labeled leukocyte scintigraphy in suspected orthopedic prosthesis
infection: comparison with other imaging modalities. Radiology 1988;168(1):235239.
(64) Mahomed NN, Barrett J, Katz JN, Baron JA, Wright J, Losina E. Epidemiology
of total knee replacement in the United States Medicare population. J Bone Joint
Surg Am 2005;87(6):1222-1228.
(65) Malhotra R, Morgan DA. Role of core biopsy in diagnosing infection before
revision hip arthroplasty. J Arthroplasty 2004;19(1):78-87.
(66) Mason JB, Fehring TK, Odum SM, Griffin WL, Nussman DS. The value of white
blood cell counts before revision total knee arthroplasty. J Arthroplasty
2003;18(8):1038-1043.
(67) Mulamba L, Ferrant A, Leners N, de NP, Rombouts JJ, Vincent A. Indium-111
leucocyte scanning in the evaluation of painful hip arthroplasty. Acta Orthop
Scand 1983;54(5):695-697.
(68) Mulcahy DM, Fenelon GC, McInerney DP. Aspiration arthrography of the hip
joint. Its uses and limitations in revision hip surgery. J Arthroplasty
1996;11(1):64-68.
(69) Mulrow C.D., Cook D.J., Davidoff F. Systematic Reviews:critical links in the
great chain of evidence. Ann Intern Med 1997;126(5):389-391.
(70) Murdoch DR, Roberts SA, Fowler JV, Jr. et al. Infection of orthopedic prostheses
after Staphylococcus aureus bacteremia. Clin Infect Dis 2001;32(4):647-649.
(71) Murphy MK, Black LA, Lamping DL, McKee CM, Sanderson C.F., Askam J.
Consensus development methods, and their use in clinical guideline development.
Health Technol Assess 1998.
(72) Murray RP, Bourne MH, Fitzgerald RH, Jr. Metachronous infections in patients
who have had more than one total joint arthroplasty. J Bone Joint Surg Am
1991;73(10):1469-1474.
232
v0.1 03.25.10
(73) Nagoya S, Kaya M, Sasaki M, Tateda K, Yamashita T. Diagnosis of periprosthetic infection at the hip using triple-phase bone scintigraphy. J Bone Joint
Surg Br 2008;90(2):140-144.
(74) Niskanen RO, Korkala OL, Haapala J, Kuokkanen HO, Kaukonen JP, Salo SA.
Drainage is of no use in primary uncomplicated cemented hip and knee
arthroplasty for osteoarthritis: a prospective randomized study. J Arthroplasty
2000;15(5):567-569.
(75) Nunez LV, Buttaro MA, Morandi A, Pusso R, Piccaluga F. Frozen sections of
samples taken intraoperatively for diagnosis of infection in revision hip surgery.
Acta Orthop 2007;78(2):226-230.
(76) Ong KL, Kurtz SM, Lau E, Bozic KJ, Berry DJ, Parvizi J. Prosthetic Joint
Infection Risk After Total Hip Arthroplasty in the Medicare Population. J
Arthroplasty 2009.
(77) Ovadia D, Luger E, Bickels J, Menachem A, Dekel S. Efficacy of closed wound
drainage after total joint arthroplasty. A prospective randomized study. J
Arthroplasty 1997;12(3):317-321.
(78) Parvizi J, Ghanem E, Menashe S, Barrack RL, Bauer TW. Periprosthetic
infection: what are the diagnostic challenges? J Bone Joint Surg Am 2006;88
Suppl 4:138-147.
(79) Peersman G, Laskin R, Davis J, Peterson M. The Insall award paper: Infection in
total knee replacement: A retrospective review of 6489 total knee replacements.
Clinical orthopaedics and related research 2001;-(392):15-23.
(80) Pepe MS, Janes H, Longton G, Leisenring W, Newcomb P. Limitations of the
odds ratio in gauging the performance of a diagnostic, prognostic, or screening
marker. Am J Epidemiol 2004;159(9):882-890.
(81) Petitti DB, Teutsch SM, Barton MB, Sawaya GF, Ockene JK, DeWitt T. Update
on the methods of the U.S. Preventive Services Task Force: insufficient evidence.
Ann Intern Med 2009;150(3):199-205.
(82) Phillips CB, Barrett JA, Losina E et al. Incidence rates of dislocation, pulmonary
embolism, and deep infection during the first six months after elective total hip
replacement. J Bone Joint Surg Am 2003;85-A(1):20-26.
(83) Pill SG, Parvizi J, Tang PH et al. Comparison of fluorodeoxyglucose positron
emission tomography and (111)indium-white blood cell imaging in the diagnosis
of periprosthetic infection of the hip. J Arthroplasty 2006;21(6 Suppl 2):91-97.
(84) Pons M, Angles F, Sanchez C et al. Infected total hip arthroplasty--the value of
intraoperative histology. Int Orthop 1999;23(1):34-36.
233
v0.1 03.25.10
(85) Pring DJ, Henderson RG, Rivett AG, Krausz T, Coombs RR, Lavender JP.
Autologous granulocyte scanning of painful prosthetic joints. J Bone Joint Surg
Br 1986;68(4):647-652.
(86) Pulido L, Ghanem E, Joshi A, Purtill JJ, Parvizi J. Periprosthetic joint infection:
the incidence, timing, and predisposing factors. Clin Orthop Relat Res
2008;466(7):1710-1715.
(87) Rand JA, Brown ML. The value of indium 111 leukocyte scanning in the
evaluation of painful or infected total knee arthroplasties. Clin Orthop Relat Res
1990;(259):179-182.
(88) Reing CM, Richin PF, Kenmore PI. Differential bone-scanning in the evaluation
of a painful total joint replacement. J Bone Joint Surg Am 1979;61(6A):933-936.
(89) Reitsma JB, Glas AS, Rutjes AW, Scholten RJ, Bossuyt PM, Zwinderman AH.
Bivariate analysis of sensitivity and specificity produces informative summary
measures in diagnostic reviews. J Clin Epidemiol 2005;58(10):982-990.
(90) Richman R. Erratum. J Arthroplasty 2009;24(8):1293.
(91) Ritter MA, Keating EM, Faris PM. Closed wound drainage in total hip or total
knee replacement. A prospective, randomized study. J Bone Joint Surg Am
1994;76(1):35-38.
(92) Saleh K, Olson M, Resig S et al. Predictors of wound infection in hip and knee
joint replacement: results from a 20 year surveillance program. J Orthop Res
2002;20(3):506-515.
(93) Savarino L, Baldini N, Tarabusi C, Pellacani A, Giunti A. Diagnosis of infection
after total hip replacement. J Biomed Mater Res B Appl Biomater 2004;70(1):139145.
(94) Schafer P, Fink B, Sandow D, Margull A, Berger I, Frommelt L. Prolonged
Bacterial Culture to Identify Late Periprosthetic Joint Infection: A Promising
Strategy. Clin Infect Dis 2008.
(95) Scher DM, Pak K, Lonner JH, Finkel JE, Zuckerman JD, Di Cesare PE. The
predictive value of indium-111 leukocyte scans in the diagnosis of infected total
hip, knee, or resection arthroplasties. J Arthroplasty 2000;15(3):295-300.
(96) Schinsky MF, la Valle CJ, Sporer SM, Paprosky WG. Perioperative testing for
joint infection in patients undergoing revision total hip arthroplasty. J Bone Joint
Surg Am 2008;90(9):1869-1875.
(97) Segura AB, Munoz A, Brulles YR et al. What is the role of bone scintigraphy in
the diagnosis of infected joint prostheses? Nucl Med Commun 2004;25(5):527532.
234
v0.1 03.25.10
(98) Smabrekke A, Espehaug B, Havelin LI, Furnes O. Operating time and survival of
primary total hip replacements: an analysis of 31,745 primary cemented and
uncemented total hip replacements from local hospitals reported to the Norwegian
Arthroplasty Register 1987-2001. Acta Orthop Scand 2004;75(5):524-532.
(99) Spangehl MJ, Masri BA, O'Connell JX, Duncan CP. Prospective analysis of
preoperative and intraoperative investigations for the diagnosis of infection at the
sites of two hundred and two revision total hip arthroplasties. J Bone Joint Surg
Am 1999;81(5):672-683.
(100) Spangehl MJ, Masterson E, Masri BA, O'Connell JX, Duncan CP. The role of
intraoperative gram stain in the diagnosis of infection during revision total hip
arthroplasty. J Arthroplasty 1999;14(8):952-956.
(101) Sudanese A, Toni A, Busanelli L et al. Diagnostic protocol in prosthetic
loosening. Chir Organi Mov 1994;79(4):257-267.
(102) Teller RE, Christie MJ, Martin W, Nance EP, Haas DW. Sequential indiumlabeled leukocyte and bone scans to diagnose prosthetic joint infection. Clin
Orthop Relat Res 2000;(373):241-247.
(103) Trampuz A, Hanssen AD, Osmon DR, Mandrekar J, Steckelberg JM, Patel R.
Synovial fluid leukocyte count and differential for the diagnosis of prosthetic
knee infection. Am J Med 2004;117(8):556-562.
(104) Trampuz A, Piper KE, Hanssen AD et al. Sonication of explanted prosthetic
components in bags for diagnosis of prosthetic joint infection is associated with
risk of contamination. J Clin Microbiol 2006;44(2):628-631.
(105) Trampuz A, Piper KE, Jacobson MJ et al. Sonication of removed hip and knee
prostheses for diagnosis of infection. N Engl J Med 2007;357(7):654-663.
(106) Virolainen P, Lahteenmaki H, Hiltunen A, Sipola E, Meurman O, Nelimarkka O.
The reliability of diagnosis of infection during revision arthroplasties. Scand J
Surg 2002;91(2):178-181.
(107) Walmsley PJ, Kelly MB, Hill RM, Brenkel I. A prospective, randomised,
controlled trial of the use of drains in total hip arthroplasty. J Bone Joint Surg Br
2005;87(10):1397-1401.
(108) Whiting P, Rutjes AW, Dinnes J, Reitsma J, Bossuyt PM, Kleijnen J.
Development and validation of methods for assessing the quality of diagnostic
accuracy studies. Health Technol Assess 2004;8(25):iii, 1-iii234.
(109) Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. The development of
QUADAS: a tool for the quality assessment of studies of diagnostic accuracy
included in systematic reviews. BMC Med Res Methodol 2003;3:25.
235
v0.1 03.25.10
(110) Whiting PF, Weswood ME, Rutjes AW, Reitsma JB, Bossuyt PN, Kleijnen J.
Evaluation of QUADAS, a tool for the quality assessment of diagnostic accuracy
studies. BMC Med Res Methodol 2006;6:9.
(111) Williams JL, Norman P, Stockley I. The value of hip aspiration versus tissue
biopsy in diagnosing infection before exchange hip arthroplasty surgery. J
Arthroplasty 2004;19(5):582-586.
(112) Wymenga AB, van H, Jr., Theeuwes A, Muytjens HL, Slooff TJ. Perioperative
factors associated with septic arthritis after arthroplasty. Prospective multicenter
study of 362 knee and 2,651 hip operations. Acta Orthop Scand 1992;63(6):665671.
236
v0.1 03.25.10
ARTICLES EXCLUDED FROM THE SYSTEMATIC REVIEW(S)
Abdul-Karim FW, McGinnis MG, Kraay M, Emancipator SN, Goldberg V. Frozen
section biopsy assessment for the presence of polymorphonuclear leukocytes in patients
undergoing revision of arthroplasties. Mod Pathol 1998;11(5):427-431.
Abudu A, Sivardeen KA, Grimer RJ, Pynsent PB, Noy M. The outcome of perioperative
wound infection after total hip and knee arthroplasty. Int Orthop 2002;26(1):40-43.
Abuzakuk T, Senthil K, V, Shenava Y et al. Autotransfusion drains in total knee
replacement. Are they alternatives to homologous transfusion? Int Orthop
2007;31(2):235-239.
Achong DM, Oates E. The computer-generated bone marrow subtraction image: a
valuable adjunct to combined In-111 WBC/Tc-99m in sulfur colloid scintigraphy for
musculoskeletal infection. Clin Nucl Med 1994;19(3):188-193.
Ahlberg A, Lunden A. Secondary operations after knee joint replacement. Clin Orthop
Relat Res 1981;(156):170-174.
Ahnfelt L, Herberts P, Malchau H, Andersson GB. Prognosis of total hip replacement. A
Swedish multicenter study of 4,664 revisions. Acta Orthop Scand Suppl 1990;238:1-26.
Ahnfelt L, Malchau H, Herberts P. The role of different infection prophylaxis studied in
the Swedish national total hip register. Acta Orthopaedica Scandinavica, Supplement
1991;62(246):6.
Ainscow DA, Denham RA. The risk of haematogenous infection in total joint
replacements. J Bone Joint Surg Br 1984;66(4):580-582.
Akre K, Signorello LB, Engstrand L et al. Risk for gastric cancer after antibiotic
prophylaxis in patients undergoing hip replacement. Cancer Res 2000;60(22):6376-6380.
AlBuhairan B, Hind D, Hutchinson A. Antibiotic prophylaxis for wound infections in
total joint arthroplasty: a systematic review. J Bone Joint Surg Br 2008;90(7):915-919.
Ali F, Wilkinson JM, Cooper JR et al. Accuracy of joint aspiration for the preoperative
diagnosis of infection in total hip arthroplasty. J Arthroplasty 2006;21(2):221-226.
Aliabadi P, Tumeh SS, Weissman BN, McNeil BJ. Cemented total hip prosthesis:
radiographic and scintigraphic evaluation. Radiology 1989;173(1):203-206.
Amin A, Watson A, Mangwani J, Nawabi D, Ahluwalia R, Loeffler M. A prospective
randomised controlled trial of autologous retransfusion in total knee replacement. J Bone
Joint Surg Br 2008;90(4):451-454.
Amin AK, Patton JT, Cook RE, Brenkel IJ. Does obesity influence the clinical outcome
at five years following total knee replacement for osteoarthritis? J Bone Joint Surg Br
2006;88(3):335-340.
237
v0.1 03.25.10
Amos RS, Constable TJ, Crockson RA, Crockson AP, McConkey B. Rheumatoid
arthritis: relation of serum C-reactive protein and erythrocyte sedimentation rates to
radiographic changes. Br Med J 1977;1(6055):195-197.
Andrew JG, Palan J, Kurup HV, Gibson P, Murray DW, Beard DJ. Obesity in total hip
replacement. J Bone Joint Surg Br 2008;90(4):424-429.
Andrews HJ, Arden GP, Hart GM, Owen JW. Deep infection after total hip replacement.
J Bone Joint Surg Br 1981;63-B(1):53-57.
Asensio A, Ramos A, Munez E, Vilanova JL, Torrijos P, Garcia FJ. Preoperative low
molecular weight heparin as venous thromboembolism prophylaxis in patients at risk for
prosthetic infection after knee arthroplasty. Infect Control Hosp Epidemiol
2005;26(12):903-909.
Athanasou NA, Pandey R, de SR, Crook D, Smith PM. Diagnosis of infection by frozen
section during revision arthroplasty. J Bone Joint Surg Br 1995;77(1):28-33.
Atkins BL, Athanasou N, Deeks JJ et al. Prospective evaluation of criteria for
microbiological diagnosis of prosthetic-joint infection at revision arthroplasty. Journal of
Clinical Microbiology 1998;36(10):2932-2939.
Austin MS, Ghanem E, Joshi A, Lindsay A, Parvizi J. A simple, cost-effective screening
protocol to rule out periprosthetic infection. J Arthroplasty 2008;23(1):65-68.
Bach CM, Sturmer R, Nogler M, Wimmer C, Biedermann R, Krismer M. Total knee
arthroplasty infection: significance of delayed aspiration. J Arthroplasty 2002;17(5):615618.
Bahebeck J, Eone DH, Nonga BN, Kingue TN, Sosso M. Implant orthopaedic surgery in
HIV asymptomatic carriers: Management and early outcome. Injury 2009.
Baker S, Fraise AP. Use of Sentinel blood culture system for analysis of specimens from
potentially infected prosthetic joints. J Clin Pathol 1994;47(5):475-476.
Baratelli M, Cabitza P, Parrini L. Ultrasonography in the investigation of loose hip
prostheses. Ital J Orthop Traumatol 1986;12(1):77-83.
Bare J, MacDonald SJ, Bourne RB. Preoperative evaluations in revision total knee
arthroplasty. Clin Orthop Relat Res 2006;446:40-44.
Barnes S, Salemi C, Fithian D et al. An enhanced benchmark for prosthetic joint
replacement infection rates. Am J Infect Control 2006;34(10):669-672.
Barrack RL, Jennings RW, Wolfe MW, Bertot AJ. The value of preoperative aspiration
before total knee revision. Clinical orthopaedics and related research 1997;-(345):8-16.
238
v0.1 03.25.10
Barrack RL, Aggarwal A, Burnett RS et al. The fate of the unexpected positive
intraoperative cultures after revision total knee arthroplasty. J Arthroplasty 2007;22(6
Suppl 2):94-99.
Bauer GC, Lindberg L, Naversten Y, Sjostrand LO. 85Sr radionuclide scintimetry in
infected total hip arthroplasty. Acta Orthop Scand 1973;44(4):439-450.
Bauer TW, Brooks PJ, Sakai H, Krebs V, Borden L. A diagnostic algorithm for detecting
an infected hip arthroplasty. Orthopedics 2003;26(9):929-930.
Becker W, Palestro CJ, Winship J et al. Rapid imaging of infections with a monoclonal
antibody fragment (LeukoScan). Clin Orthop Relat Res 1996;(329):263-272.
Bedi HS, Fletcher SF, Rush JH, Choong PF. An audit of early hospital readmission after
primary knee joint replacement. Aust N Z J Surg 1997;67(6):340-342.
Bengtson S, Knutson K. The infected knee arthroplasty. A 6-year follow-up of 357 cases.
Acta Orthop Scand 1991;62(4):301-311.
Benson MK, Hughes SP. Infection following total hip replacement in a general hospital
without special orthopaedic facilities. Acta Orthop Scand 1975;46(6):968-978.
Berend KR, Lombardi AV, Jr., Adams JB. Unexpected positive intraoperative cultures
and gram stain in revision total hip arthroplasty for presumed aseptic failure. Orthopedics
2007;30(12):1051-1053.
Bergstrom B, Lidgren L, Lindberg L. Radiographic abnormalities caused by
postoperative infection following total hip arthroplasty. Clin Orthop Relat Res
1974;(99):95-102.
Berquist TH, Bender CE, Maus TP, Ward EM, Rand JA. Pseudobursae: a useful finding
in patients with painful hip arthroplasty. AJR Am J Roentgenol 1987;148(1):103-106.
Beyer CA, Hanssen AD, Lewallen DG, Pittelkow MR. Primary total knee arthroplasty in
patients with psoriasis. J Bone Joint Surg Br 1991;73(2):258-259.
Bindelglass DF, Pellegrino J. The role of blood cultures in the acute evaluation of
postoperative fever in arthroplasty patients. J Arthroplasty 2007;22(5):701-702.
Blom AW, Brown J, Taylor AH, Pattison G, Whitehouse S, Bannister GC. Infection after
total knee arthroplasty. J Bone Joint Surg Br 2004;86(5):688-691.
Bohm P, Holy T. Is there a future for hinged prostheses in primary total knee
arthroplasty? A 20-year survivorship analysis of the Blauth prosthesis. J Bone Joint Surg
Br 1998;80(2):302-309.
Bong MR, Di Cesare PE. Stiffness after total knee arthroplasty. J Am Acad Orthop Surg
2004;12(3):164-171.
239
v0.1 03.25.10
Bongartz T, Halligan CS, Osmon DR et al. Incidence and risk factors of prosthetic joint
infection after total hip or knee replacement in patients with rheumatoid arthritis.
Arthritis Rheum 2008;59(12):1713-1720.
Bori G, Soriano A, Garcia S et al. Low sensitivity of histology to predict the presence of
microorganisms in suspected aseptic loosening of a joint prosthesis. Mod Pathol
2006;19(6):874-877.
Bosch P, Kristen H, Zweymuller K. An analysis of 119 loosenings in total hip
endoprostheses. Archives of Orthopaedic and Traumatic Surgery 1980;96(2):83-90.
Bottner F, Wegner A, Winkelmann W, Becker K, Erren M, Gotze C. Interleukin-6,
procalcitonin and TNF-(alpha). Journal of Bone and Joint Surgery - Series B
2007;89(1):94-99.
Boubaker A, Delaloye AB, Blanc CH, Dutoit M, Leyvraz PF, Delaloye B.
Immunoscintigraphy with antigranulocyte monoclonal antibodies for the diagnosis of
septic loosening of hip prostheses. Eur J Nucl Med 1995;22(2):139-147.
Bourne RB, Rorabeck CH, Ghazal ME, Lee MH. Pain in the thigh following total hip
replacement with a porous-coated anatomic prosthesis for osteoarthrosis. A five-year
follow-up study. J Bone Joint Surg Am 1994;76(10):1464-1470.
Bozic KJ, Kurtz SM, Lau E et al. The Epidemiology of Revision Total Knee Arthroplasty
in the United States. Clin Orthop Relat Res 2009.
Brander VA, David SS, Adams AD et al. Predicting Total Knee Replacement Pain: A
Prospective, Observational Study. Clinical orthopaedics and related research 2003;(416):27-36.
Bratzler DW, Houck PM. Antimicrobial prophylaxis for surgery: An advisory statement
from the national surgical infection prevention project. Clinical Infectious Diseases
2004;38(12):1706-1715.
Bratzler DW, Houck PM. Antimicrobial prophylaxis for surgery: An advisory statement
from the National Surgical Infection Prevention Project. American Journal of Surgery
2005;189(4):395-404.
Brause BD. Infected total knee replacement: diagnostic, therapeutic, and prophylactic
considerations. Orthop Clin North Am 1982;13(1):245-249.
Britton KE, Vinjamuri S, Hall AV et al. Clinical evaluation of technetium-99m infecton
for the localisation of bacterial infection. Eur J Nucl Med 1997;24(5):553-556.
Brown AR, Taylor GJ, Gregg PJ. Air contamination during skin preparation and draping
in joint replacement surgery. J Bone Joint Surg Br 1996;78(1):92-94.
240
v0.1 03.25.10
Buchholz HW, Elson RA, Engelbrecht E, Lodenkamper H, Rottger J, Siegel A.
Management of deep infection of total hip replacement. J Bone Joint Surg Br 1981;63B(3):342-353.
Byrne AM, Morris S, McCarthy T, Quinlan W, O'byrne JM. Outcome following deep
wound contamination in cemented arthroplasty. Int Orthop 2007;31(1):27-31.
Cain TM, Fon GT, Brumby S, Howie DW. Plain film and arthrographic findings in
painful total hip arthroplasties with surgical correlation. Australas Radiol
1990;34(3):211-218.
Cameron HU. Knee effusion after total knee replacement. Can Fam Physician
1993;39:1107-1115.
Canner GC, Steinberg ME, Heppenstall RB, Balderston R. The infected hip after total hip
arthroplasty. J Bone Joint Surg Am 1984;66(9):1393-1399.
Carlsson AS. Erythrocyte sedimentation rate in infected and non-infected total-hip
arthroplasties. Acta Orthop Scand 1978;49(3):287-290.
Carlsson AS. 351 total hip replacements according to Charnley. A review of
complications and function. Acta Orthop Scand 1981;52(3):339-344.
Chacko TK, Zhuang H, Stevenson K, Moussavian B, Alavi A. The importance of the
location of fluorodeoxyglucose uptake in periprosthetic infection in painful hip
prostheses. Nucl Med Commun 2002;23(9):851-855.
Chacko TK, Zhuang H, Nakhoda KZ, Moussavian B, Alavi A. Applications of
fluorodeoxyglucose positron emission tomography in the diagnosis of infection. Nucl
Med Commun 2003;24(6):615-624.
Chafetz N, Hattner RS, Ruarke WC, Helms CA, Genant HK, Murray WR. Multinuclide
digital subtraction imaging in symptomatic prosthetic joints. AJR Am J Roentgenol
1985;144(6):1255-1258.
Chan CL, Villar RN. Obesity and quality of life after primary hip arthroplasty. J Bone
Joint Surg Br 1996;78(1):78-81.
Chan PKH, Brenkel IJ, Aderinto J. The outcome of total hip arthroplasty in diabetes
mellitus. British Journal of Diabetes and Vascular Disease 2005;5(3):146-149.
Charnley J. Postoperative infection after total hip replacement with special reference to
air contamination in the operating room. Clin Orthop Relat Res 1972;87:167-187.
Charosky CB, Bullough PG, Wilson PD, Jr. Total hip replacement failures. A histological
evaluation. J Bone Joint Surg Am 1973;55(1):49-58.
241
v0.1 03.25.10
Cherney DL, Amstutz HC. Total hip replacement in the previously septic hip. J Bone
Joint Surg Am 1983;65(9):1256-1265.
Chesney D, Sales J, Elton R, Brenkel IJ. Infection after knee arthroplasty a prospective
study of 1509 cases. J Arthroplasty 2008;23(3):355-359.
Cheung A, Lachiewicz PF, Renner JB. The role of aspiration and contrast-enhanced
arthrography in evaluating the uncemented hip arthroplasty. AJR Am J Roentgenol
1997;168(5):1305-1309.
Chevillotte CJ, Ali MH, Trousdale RT, Larson DR, Gullerud RE, Berry DJ.
Inflammatory Laboratory Markers in Periprosthetic Hip Fractures. J Arthroplasty 2008.
Chiew YF, Theis JC. Comparison of infection rate using different methods of assessment
for surveillance of total hip replacement surgical site infections. ANZ J Surg
2007;77(7):535-539.
Chik KK, Magee MA, Bruce WJ et al. Tc-99m stannous colloid-labeled leukocyte
scintigraphy in the evaluation of the painful arthroplasty. Clin Nucl Med
1996;21(11):838-843.
Chimento GF, Finger S, Barrack RL. Gram stain detection of infection during revision
arthroplasty. J Bone Joint Surg Br 1996;78(5):838-839.
Chodak GW, Plaut ME. Use of systemic antibiotics for prophylaxis in surgery: a critical
review. Arch Surg 1977;112(3):326-334.
Choong PF, Dowsey MM, Carr D, Daffy J, Stanley P. Risk factors associated with acute
hip prosthetic joint infections and outcome of treatment with a rifampinbased regimen.
Acta Orthop 2007;78(6):755-765.
Choudhry RR, Rice RP, Triffitt PD, Harper WM, Gregg PJ. Plasma viscosity and Creactive protein after total hip and knee arthroplasty. J Bone Joint Surg Br
1992;74(4):523-524.
Clarke MT, Roberts CP, Lee PT, Gray J, Keene GS, Rushton N. Polymerase chain
reaction can detect bacterial DNA in aseptically loose total hip arthroplasties. Clin
Orthop Relat Res 2004;(427):132-137.
Clements ACA, Tong ENC, Morton AP, Whitby M. Risk stratification for surgical site
infections in Australia: evaluation of the US National Nosocomial Infection Surveillance
risk index. Journal of Hospital Infection 2007;66(2):148-155.
Coello R, Charlett A, Wilson J, Ward V, Pearson A, Borriello P. Adverse impact of
surgical site infections in English hospitals. J Hosp Infect 2005;60(2):93-103.
242
v0.1 03.25.10
Cooper HJ, Ranawat AS, Potter HG, Foo LF, Jawetz ST, Ranawat CS. Magnetic
Resonance Imaging in the Diagnosis and Management of Hip Pain After Total Hip
Arthroplasty. J Arthroplasty 2008.
Covey DC, Albright JA. Clinical significance of the erythrocyte sedimentation rate in
orthopaedic surgery. J Bone Joint Surg Am 1987;69(1):148-151.
Crokaert F, Schoutens A, Wagner J, Ansay J. Gallium-67 citrate as an aid to the
diagnosis of infection in hip surgery. Int Orthop 1982;6(3):163-169.
Cune J, Soriano A, Martinez JC, Garcia S, Mensa J. A superficial swab culture is useful
for microbiologic diagnosis in acute prosthetic joint infections. Clin Orthop Relat Res
2009;467(2):531-535.
Dams ET, Oyen WJ, Boerman OC et al. 99mTc-PEG liposomes for the scintigraphic
detection of infection and inflammation: clinical evaluation. J Nucl Med 2000;41(4):622630.
Datz FL, Thorne DA. Effect of antibiotic therapy on the sensitivity of indium-111-labeled
leukocyte scans. J Nucl Med 1986;27(12):1849-1853.
Datz FL, Anderson CE, Ahluwalia R et al. The efficacy of indium-111-polyclonal IgG
for the detection of infection and inflammation. J Nucl Med 1994;35(1):74-83.
de Lima Ramos PA, Martin-Comin J, Bajen MT et al. Simultaneous administration of
99Tcm-HMPAO-labelled autologous leukocytes and 111In-labelled non-specific
polyclonal human immunoglobulin G in bone and joint infections. Nucl Med Commun
1996;17(9):749-757.
de LF, Novelli A, Pellizzer G et al. Regional and systemic prophylaxis with teicoplanin
in monolateral and bilateral total knee replacement procedures: study of
pharmacokinetics and tissue penetration. Antimicrob Agents Chemother
1993;37(12):2693-2698.
de WF, van de Wiele C, Vogelaers D, de SK, Verdonk R, Dierckx RA. Fluorine-18
fluorodeoxyglucose-position emission tomography: a highly accurate imaging modality
for the diagnosis of chronic musculoskeletal infections. J Bone Joint Surg Am 2001;83A(5):651-660.
Della Valle CJ, Scher DM, Kim YH et al. The role of intraoperative Gram stain in
revision total joint arthroplasty. J Arthroplasty 1999;14(4):500-504.
Della Valle CJ, Bogner E, Desai P et al. Analysis of frozen sections of intraoperative
specimens obtained at the time of reoperation after hip or knee resection arthroplasty for
the treatment of infection. J Bone Joint Surg Am 1999;81(5):684-689.
Della Valle CJ, Zuckerman JD, Di Cesare PE. Periprosthetic sepsis. Clin Orthop Relat
Res 2004;(420):26-31.
243
v0.1 03.25.10
Demirkol MO, Adalet I, Unal SN, Tozun R, Cantez S. 99Tc(m)-polyclonal IgG
scintigraphy in the detection of infected hip and knee prostheses. Nucl Med Commun
1997;18(6):543-548.
Dennis DA. Evaluation of painful total knee arthroplasty. J Arthroplasty 2004;19(4 Suppl
1):35-40.
Deshmukh RG, Hayes JH, Pinder IM. Does body weight influence outcome after total
knee arthroplasty? A 1-year analysis. J Arthroplasty 2002;17(3):315-319.
Devillers A, Moisan A, Jean S, Arvieux C, Bourguet P. Technetium-99m
hexamethylpropylene amine oxime leucocyte scintigraphy for the diagnosis of bone and
joint infections: a retrospective study in 116 patients. Eur J Nucl Med 1995;22(4):302307.
Dobbins JJ, Seligson D, Raff MJ. Bacterial colonization of orthopedic fixation devices in
the absence of clinical infection. J Infect Dis 1988;158(1):203-205.
Dowsey MM, Choong PF. Early outcomes and complications following joint arthroplasty
in obese patients: a review of the published reports. ANZ J Surg 2008;78(6):439-444.
Dowsey MM, Choong PF. Obesity is a major risk factor for prosthetic infection after
primary hip arthroplasty. Clin Orthop Relat Res 2008;466(1):153-158.
Drancourt M, Argenson JN, Tissot DH, Aubaniac JM, Raoult D. Psoriasis is a risk factor
for hip-prosthesis infection. Eur J Epidemiol 1997;13(2):205-207.
Drinkwater CJ, Neil MJ. Optimal timing of wound drain removal following total joint
arthroplasty. J Arthroplasty 1995;10(2):185-189.
Duff GP, Lachiewicz PF, Kelley SS. Aspiration of the knee joint before revision
arthroplasty. Clin Orthop Relat Res 1996;(331):132-139.
Duffy P, Masri BA, Garbuz D, Duncan CP. Evaluation of patients with pain following
total hip replacement. Instr Course Lect 2006;55:223-232.
Duffy PJ, Masri BA, Garbuz DS, Duncan CP. Evaluation of patients with pain following
total hip replacement. Journal of Bone and Joint Surgery - Series A 2005;87(11):25662575.
Dupont C, Rodenbach J, Flachaire E. The value of C-reactive protein for postoperative
monitoring of lower limb arthroplasty. Ann Readapt Med Phys 2008;51(5):348-357.
Dupont JA. Significance of operative cultures in total hip arthroplasty. Clin Orthop Relat
Res 1986;(211):122-127.
Dussault RG, Goldman AB, Ghelman B. Radiologic diagnosis of loosening and infection
in hip prostheses. J Can Assoc Radiol 1977;28(2):119-123.
244
v0.1 03.25.10
Edwards C, Counsell A, Boulton C, Moran CG. Early infection after hip fracture surgery:
risk factors, costs and outcome. J Bone Joint Surg Br 2008;90(6):770-777.
Ehrenkranz NJ. Surgical wound infection occurrence in clean operations; risk
stratification for interhospital comparisons. Am J Med 1981;70(4):909-914.
El E, I, Blondet C, Moullart V et al. The usefulness of 99mTc sulfur colloid bone marrow
scintigraphy combined with 111In leucocyte scintigraphy in prosthetic joint infection.
Nucl Med Commun 2004;25(2):171-175.
Engesaeter LB, Espehaug B, Lie SA, Furnes O, Havelin LI. Does cement increase the
risk of infection in primary total hip arthroplasty? Revision rates in 56,275 cemented and
uncemented primary THAs followed for 0-16 years in the Norwegian Arthroplasty
Register. Acta Orthop 2006;77(3):351-358.
Ericson C, Lidgren L, Lindberg L. Cloxacillin in the prophylaxis of postoperative
infections of the hip. J Bone Joint Surg Am 1973;55(4):808-13, 843.
Eshkenazi AU, Garti A, Tamir L, Hendel D. Serum and synovial vancomycin
concentrations following prophylactic administration in knee arthroplasty. Am J Knee
Surg 2001;14(4):221-223.
Espehaug B, Havelin LI, Engesaeter LB, Langeland N, Vollset SE. Patient-related risk
factors for early revision of total hip replacements. A population register-based casecontrol study of 674 revised hips. Acta Orthop Scand 1997;68(3):207-215.
Espehaug B, Engesaeter LB, Vollset SE, Havelin LI, Langeland N. Antibiotic
prophylaxis in total hip arthroplasty. Journal of Bone and Joint Surgery - Series B
1997;79(4):590-595.
Fan JC, Hung HH, Fung KY. Infection in primary total knee replacement. Hong Kong
Med J 2008;14(1):40-45.
Fehring TK, Cohen B. Aspiration as a guide to sepsis in revision total hip arthroplasty. J
Arthroplasty 1996;11(5):543-547.
Feith R, Slooff TJ, Kazem I, van Rens TJ. Strontium 87mSr bone scanning for the
evaluation of total hip replacement. J Bone Joint Surg Br 1976;58(1):79-83.
Feldman DS, Lonner JH, Desai P, Zuckerman JD. The role of intraoperative frozen
sections in revision total joint arthroplasty. J Bone Joint Surg Am 1995;77(12):18071813.
Fender D, Harper WM, Gregg PJ. Outcome of Charnley total hip replacement across a
single health region in England: the results at five years from a regional hip register. J
Bone Joint Surg Br 1999;81(4):577-581.
245
v0.1 03.25.10
Fernandez AM, Gomez-Sancha F, Peinado IF, Herruzo CR. Risk infection factors in the
total hip replacement. Eur J Epidemiol 1997;13(4):443-446.
Fitzgerald Jr RH, Peterson LFA, Washington II JA. Bacterial colonization of wounds and
sepsis in total hip arthroplasty. Journal of Bone and Joint Surgery - Series A
1973;55(6):1242-1250.
Fitzgerald RH, Jr., Peterson LF, Washington JA, Van Scoy RE, Coventry MB. Bacterial
colonization of wounds and sepsis in total hip arthroplasty. J Bone Joint Surg Am
1973;55(6):1242-1250.
Fitzgerald RH, Jr., Nolan DR, Ilstrup DM, Van Scoy RE, Washington JA, Coventry MB.
Deep wound sepsis following total hip arthroplasty. J Bone Joint Surg Am
1977;59(7):847-855.
Flivik G, Sloth M, Rydholm U, Herrlin K, Lidgren L. Technetium-99m-nanocolloid
scintigraphy in orthopedic infections: a comparison with indium-111-labeled leukocytes.
J Nucl Med 1993;34(10):1646-1650.
Foldes K, Gaal M, Balint P et al. Ultrasonography after hip arthroplasty. Skeletal Radiol
1992;21(5):297-299.
Foran JR, Mont MA, Etienne G, Jones LC, Hungerford DS. The outcome of total knee
arthroplasty in obese patients. J Bone Joint Surg Am 2004;86-A(8):1609-1615.
Foran JR, Mont MA, Rajadhyaksha AD, Jones LC, Etienne G, Hungerford DS. Total
knee arthroplasty in obese patients: a comparison with a matched control group. J
Arthroplasty 2004;19(7):817-824.
Forster IW, Crawford R. Sedimentation rate in infected and uninfected total hip
Frank KL, Hanssen AD, Patel R. icaA is not a useful diagnostic marker for prosthetic
joint infection. J Clin Microbiol 2004;42(10):4846-4849.
Fulkerson E, Valle CJ, Wise B, Walsh M, Preston C, Di Cesare PE. Antibiotic
susceptibility of bacteria infecting total joint arthroplasty sites. J Bone Joint Surg Am
2006;88(6):1231-1237.
Furnes O, Espehaug B, Lie SA, Vollset SE, Engesaeter LB, Havelin LI. Early failures
among 7,174 primary total knee replacements: a follow-up study from the Norwegian
Arthroplasty Register 1994-2000. Acta Orthop Scand 2002;73(2):117-129.
Gaine WJ, Ramamohan NA, Hussein NA, Hullin MG, McCreath SW. Wound infection
in hip and knee arthroplasty. J Bone Joint Surg Br 2000;82(4):561-565.
246
v0.1 03.25.10
Galat DD, McGovern SC, Hanssen AD, Larson DR, Harrington JR, Clarke HD. Early
return to surgery for evacuation of a postoperative hematoma after primary total knee
arthroplasty. J Bone Joint Surg Am 2008;90(11):2331-2336.
Galat DD, McGovern SC, Larson DR, Harrington JR, Hanssen AD, Clarke HD. Surgical
treatment of early wound complications following primary total knee arthroplasty. J Bone
Joint Surg Am 2009;91(1):48-54.
Garibaldi RA, Cushing D, Lerer T. Risk factors for postoperative infection. Am J Med
1991;91(3B):158S-163S.
Garvin KL, Hanssen AD. Infection after total hip arthroplasty. Past, present, and future. J
Bone Joint Surg Am 1995;77(10):1576-1588.
Gelman MI. Arthrography in total hip prosthesis complications. AJR Am J Roentgenol
1976;126(4):743-750.
Ghanem E, Jaberi FM, Parvizi J. Periprosthetic infection in a nutshell. Am J Orthop
2007;36(10):520-525.
Ghanem E, Houssock C, Pulido L, Han S, Jaberi FM, Parvizi J. Determining "true"
leukocytosis in bloody joint aspiration. J Arthroplasty 2008;23(2):182-187.
Ghanem E, Antoci V, Jr., Pulido L, Joshi A, Hozack W, Parvizi J. The use of receiver
operating characteristics analysis in determining erythrocyte sedimentation rate and Creactive protein levels in diagnosing periprosthetic infection prior to revision total hip
arthroplasty. Int J Infect Dis 2009.
Ghanem E, Ketonis C, Restrepo C, Joshi A, Barrack R, Parvizi J. Periprosthetic infection:
where do we stand with regard to Gram stain? Acta Orthop 2009;80(1):37-40.
Gillespie WJ, Walenkamp G. Antibiotic prophylaxis for surgery for proximal femoral
and other closed long bone fractures. Cochrane Database Syst Rev 2001;(1):CD000244.
Ginai AZ, van Biezen FC, Kint PA, Oei HY, Hop WC. Digital subtraction arthrography
in preoperative evaluation of painful total hip arthroplasty. Skeletal Radiol
1996;25(4):357-363.
Glenny A, Song F. Antimicrobial prophylaxis in total hip replacement: a systematic
review. Health Technol Assess 1999;3(21):1-57.
Goergen TG, Dalinka MK, Alazraki N et al. Evaluation of the patient with painful hip or
knee arthroplasty. American College of Radiology. ACR Appropriateness Criteria.
Radiology 2000;215 Suppl:295-298.
Gomez-Luzuriaga MA, Galan V, Villar JM. Scintigraphy with Tc, Ga and In in painful
total hip prostheses. Int Orthop 1988;12(2):163-167.
247
v0.1 03.25.10
Gonzalez MH, Mekhail AO. The failed total knee arthroplasty: evaluation and etiology. J
Am Acad Orthop Surg 2004;12(6):436-446.
Gordon SM, Culver DH, Simmons BP, Jarvis WR. Risk factors for wound infections
after total knee arthroplasty. Am J Epidemiol 1990;131(5):905-916.
Gould ES, Potter HG, Bober SE. Role of routine percutaneous hip aspirations prior to
prosthesis revision. Skeletal Radiol 1990;19(6):427-430.
Grant JA, Viens N, Bolognesi MP, Olson SA, Cook CE. Two-year outcomes in primary
THA in obese male veterans administration medical center patients. Rheumatol Int
2008;28(11):1105-1109.
Gratz S, Behr TM, Reize P, Pfestroff A, Kampen WU, Hoffken H. (99m)Tc-Fab'
fragments (sulesomab) for imaging septically loosened total knee arthroplasty. J Int Med
Res 2009;37(1):54-67.
Greene KA, Wilde AH, Stulberg BN. Preoperative nutritional status of total joint
patients. Relationship to postoperative wound complications. J Arthroplasty
1991;6(4):321-325.
Guercio N, Orsini G, Broggi S, Paschero B. Arthrography of the prosthesetized painful
hip: the importance of imaging and functional testing. Ital J Orthop Traumatol
1990;16(1):93-101.
Hall AV, Solanki KK, Vinjamuri S, Britton KE, Das SS. Evaluation of the efficacy of
99mTc-Infecton, a novel agent for detecting sites of infection. J Clin Pathol
1998;51(3):215-219.
Hamilton H, Jamieson J. Deep infection in total hip arthroplasty. Can J Surg
2008;51(2):111-117.
Hanssen AD, Rand JA. Evaluation and treatment of infection at the site of a total hip or
knee arthroplasty. Journal of Bone and Joint Surgery - Series A 1998;80(6):910-922.
Henderson JJ, Bamford DJ, Noble J, Brown JD. The value of skeletal scintigraphy in
predicting the need for revision surgery in total knee replacement. Orthopedics
1996;19(4):295-299.
Hervey SL, Purves HR, Guller U, Toth AP, Vail TP, Pietrobon R. Provider Volume of
Total Knee Arthroplasties and Patient Outcomes in the HCUP-Nationwide Inpatient
Sample. J Bone Joint Surg Am 2003;85-A(9):1775-1783.
Hill C, Flamant R, Mazas F, Evrard J. Prophylactic cefazolin versus placebo in total hip
replacement. Report of a multicentre double-blind randomised trial. Lancet
1981;1(8224):795-796.
248
v0.1 03.25.10
Horberg MA, Hurley LB, Klein DB et al. Surgical outcomes in human immunodeficiency
virus-infected patients in the era of highly active antiretroviral therapy. Arch Surg
2006;141(12):1238-1245.
Horne G, Devane P, Davidson A, Adams K, Purdie G. The influence of steroid injections
on the incidence of infection following total knee arthroplasty. N Z Med J
2008;121(1268):U2896.
Hughes PW, Salvati EA, Wilson PD, Jr., Blumenfeld EL. Treatment of subacute sepsis of
the hip by antibiotics and joint replacement. Criteria for diagnosis with evaluation of
twenty-six cases. Clin Orthop Relat Res 1979;(141):143-157.
Huotari K, Lyytikainen O. Impact of postdischarge surveillance on the rate of surgical
site infection after orthopedic surgery. Infect Control Hosp Epidemiol 2006;27(12):13241329.
Ibrahim T, Hobson S, Beiri A, Esler CN. No influence of body mass index on early
outcome following total hip arthroplasty. Int Orthop 2005;29(6):359-361.
Ilstrup DM, Nolan DR, Beckenbaugh RD, Coventry MB. Factors influencing the results
in 2,012 total hip arthroplasties. Clin Orthop Relat Res 1973;(95):250-262.
Ince A, Rupp J, Frommelt L, Katzer A, Gille J, Lohr JF. Is "aseptic" loosening of the
prosthetic cup after total hip replacement due to nonculturable bacterial pathogens in
patients with low-grade infection? Clin Infect Dis 2004;39(11):1599-1603.
Iorwerth A, Wilson C, Topley N, Pallister I. Neutrophil activity in total knee
replacement: implications in preventing post-arthroplasty infection. Knee
2003;10(1):111-113.
Isacson J, Collert S. Renal impairment after high doses of dicloxacillin-prophylaxis in
joint replacement surgery. Acta Orthop Scand 1984;55(4):407-410.
Itasaka T, Kawai A, Sato T, Mitani S, Inoue H. Diagnosis of infection after total hip
arthroplasty. J Orthop Sci 2001;6(4):320-326.
Ivancevic V, Perka C, Hasart O, Sandrock D, Munz DL. Imaging of low-grade bone
infection with a technetium-99m labelled monoclonal anti-NCA-90 Fab' fragment in
patients with previous joint surgery. Eur J Nucl Med Mol Imaging 2002;29(4):547-551.
Iyengar KP, Vinjamuri S. Role of 99mTc Sulesomab in the diagnosis of prosthetic joint
infections. Nucl Med Commun 2005;26(6):489-496.
Jaberi FM, Parvizi J, Haytmanek CT, Joshi A, Purtill J. Procrastination of wound
drainage and malnutrition affect the outcome of joint arthroplasty. Clin Orthop Relat Res
2008;466(6):1368-1371.
249
v0.1 03.25.10
Jacobsen PL, Murray W. Prophylactic coverage of dental patients with artificial joints: a
retrospective analysis of thirty-three infections in hip prostheses. Oral Surg Oral Med
Oral Pathol 1980;50(2):130-133.
Jacobson JJ, Millard HD, Plezia R, Blankenship JR. Dental treatment and late prosthetic
joint infections. Oral Surg Oral Med Oral Pathol 1986;61(4):413-417.
Jain NB, Guller U, Pietrobon R, Bond TK, Higgins LD. Comorbidities increase
complication rates in patients having arthroplasty. Clin Orthop Relat Res 2005;(435):232238.
James ET, Hunter GA, Cameron HU. Total hip revision arthroplasty: does sepsis
influence the results? Clin Orthop Relat Res 1982;(170):88-94.
Jamsen E, Varonen M, Huhtala H et al. Incidence of Prosthetic Joint Infections After
Primary Knee Arthroplasty. J Arthroplasty 2008.
Jamsen E, Huotari K, Huhtala H, Nevalainen J, Konttinen YT. Low rate of infected knee
replacements in a nationwide series--is it an underestimate? Acta Orthop 2009;80(2):205212.
Jaruskova M, Belohlavek O. Role of FDG-PET and PET/CT in the diagnosis of
prolonged febrile states. Eur J Nucl Med Mol Imaging 2006;33(8):913-918.
Jensen JE, Jensen TG, Smith TK, Johnston DA, Dudrick SJ. Nutrition in orthopaedic
surgery. J Bone Joint Surg Am 1982;64(9):1263-1272.
Jensen JS, Madsen JL. Tc-99m-MDP scintigraphy not informative in painful total hip
arthroplasty. J Arthroplasty 1990;5 Suppl:S11-S13.
Jerry GJ, Jr., Rand JA, Ilstrup D. Old sepsis prior to total knee arthroplasty. Clin Orthop
Relat Res 1988;(236):135-140.
Jibodh SR, Gurkan I, Wenz S, Henze EP. In-hospital outcome and resource use in hip
arthroplasty: Influence of body mass. Orthopedics 2004;27(6):594-601.
Jiganti JJ, Goldstein WM, Williams CS. A comparison of the perioperative morbidity in
total joint arthroplasty in the obese and nonobese patient. Clin Orthop Relat Res
1993;(289):175-179.
Johnson DP, Bannister GC. The outcome of infected arthroplasty of the knee. J Bone
Joint Surg Br 1986;68(2):289-291.
Johnson DP. Antibiotic prophylaxis with cefuroxime in arthroplasty of the knee. J Bone
Joint Surg Br 1987;69(5):787-789.
Johnston DP. Antibiotic prophylaxis with cefuroxime in arthroplasty of the knee. Journal
of Bone and Joint Surgery - Series B 1987;69(5):787-789.
250
v0.1 03.25.10
Jones EC, Insall JN, Inglis AE, Ranawat CS. GUEPAR knee arthroplasty results and late
complications. Clin Orthop Relat Res 1979;(140):145-152.
Josefsson G, Kolmert L. Prophylaxis with systematic antibiotics versus gentamicin bone
cement in total hip arthroplasty. A ten-year survey of 1,688 hips. Clin Orthop Relat Res
1993;(292):210-214.
Jupiter JB, Karchmer AW, Lowell JD, Harris WH. Total hip arthroplasty in the treatment
of adult hips with current or quiescent sepsis. J Bone Joint Surg Am 1981;63(2):194-200.
Kanner WA, Saleh KJ, Frierson HF, Jr. Reassessment of the usefulness of frozen section
analysis for hip and knee joint revisions. Am J Clin Pathol 2008;130(3):363-368.
Kaspar S, de VdB. Infection in hip arthroplasty after previous injection of steroid. J Bone
Joint Surg Br 2005;87(4):454-457.
Kataoka M, Torisu T, Tsumura H, Yoshida S, Takashita M. An assessment of
histopathological criteria for infection in joint arthroplasty in rheumatoid synovium. Clin
Rheumatol 2002;21(2):159-163.
Kersey R, Benjamin J, Marson B. White blood cell counts and differential in synovial
fluid of aseptically failed total knee arthroplasty. J Arthroplasty 2000;15(3):301-304.
Kessler S, Kinkel S, Kafer W, Puhl W, Schochat T. Influence of operation duration on
perioperative morbidity in revision total hip arthroplasty. Acta Orthop Belg
2003;69(4):328-333.
Khatod M, Inacio M, Paxton EW et al. Knee replacement: epidemiology, outcomes, and
trends in Southern California: 17,080 replacements from 1995 through 2004. Acta Orthop
2008;79(6):812-819.
Khuri SF, Daley J, Henderson W et al. The National Veterans Administration Surgical
Risk Study: risk adjustment for the comparative assessment of the quality of surgical
care. J Am Coll Surg 1995;180(5):519-531.
Kim J, Nelson CL, Lotke PA. Stiffness after total knee arthroplasty. Prevalence of the
complication and outcomes of revision. J Bone Joint Surg Am 2004;86-A(7):1479-1484.
Kim Y, Morshed S, Joseph T, Bozic K, Ries MD. Clinical impact of obesity on stability
following revision total hip arthroplasty. Clin Orthop Relat Res 2006;453:142-146.
Kim YH. Total arthroplasty of the hip after childhood sepsis. J Bone Joint Surg Br
1991;73(5):783-786.
Kim YH, Kim JS, Cho SH. Total knee arthroplasty after spontaneous osseous ankylosis
and takedown of formal knee fusion. J Arthroplasty 2000;15(4):453-460.
251
v0.1 03.25.10
Kim YH, Oh SH, Kim JS. Total hip arthroplasty in adult patients who had childhood
infection of the hip. J Bone Joint Surg Am 2003;85-A(2):198-204.
Klenerman L, Seal D, Sullens K. Combined prophylactic effect of ultraclean air and
cefuroxime for reducing infection in prosthetic surgery. Acta Orthop Belg 1991;57(1):1924.
Knobben BA, Engelsma Y, Neut D, van der Mei HC, Busscher HJ, van H, Jr.
Intraoperative contamination influences wound discharge and periprosthetic infection.
Clin Orthop Relat Res 2006;452:236-241.
Knutson K, Lindstrand A, Lidgren L. Survival of knee arthroplasties. A nation-wide
multicentre investigation of 8000 cases. J Bone Joint Surg Br 1986;68(5):795-803.
Kobayashi N, Procop GW, Krebs V, Kobayashi H, Bauer TW. Molecular identification
of bacteria from aseptically loose implants. Clin Orthop Relat Res 2008;466(7):17161725.
Kurtz SM, Lau E, Schmier J, Ong KL, Zhao K, Parvizi J. Infection burden for hip and
knee arthroplasty in the United States. J Arthroplasty 2008;23(7):984-991.
Lai K, Bohm ER, Burnell C, Hedden DR. Presence of medical comorbidities in patients
with infected primary hip or knee arthroplasties. J Arthroplasty 2007;22(5):651-656.
Laiho K, Maenpaa H, Kautiainen H et al. Rise in serum C reactive protein after hip and
knee arthroplasties in patients with rheumatoid arthritis. Ann Rheum Dis 2001;60(3):275277.
Larikka MJ, Ahonen AK, Junila JA, Niemela O, Hamalainen MM, Syrjala HP. Improved
method for detecting knee replacement infections based on extended combined 99mTcwhite blood cell/bone imaging. Nucl Med Commun 2001;22(10):1145-1150.
Larikka MJ, Ahonen AK, Junila JA, Niemela O, Hamalainen MM, Syrjala HP. Extended
combined 99mTc-white blood cell and bone imaging improves the diagnostic accuracy in
the detection of hip replacement infections. Eur J Nucl Med 2001;28(3):288-293.
Larikka MJ, Ahonen AK, Niemela O et al. Comparison of 99mTc ciprofloxacin, 99mTc
white blood cell and three-phase bone imaging in the diagnosis of hip prosthesis
infections: improved diagnostic accuracy with extended imaging time. Nucl Med
Commun 2002;23(7):655-661.
Lawton RL, Morrey BF. The use of heparin in patients in whom a pulmonary embolism
is suspected after total hip arthroplasty. J Bone Joint Surg Am 1999;81(8):1063-1072.
Lazzarini L, Pellizzer G, Stecca C, Viola R, de LF. Postoperative infections following
total knee replacement: an epidemiological study. J Chemother 2001;13(2):182-187.
252
v0.1 03.25.10
Lentino JR. Prosthetic joint infections: bane of orthopedists, challenge for infectious
disease specialists. Clin Infect Dis 2003;36(9):1157-1161.
Leong G, Wilson J, Charlett A. Duration of operation as a risk factor for surgical site
infection: comparison of English and US data. J Hosp Infect 2006;63(3):255-262.
Levine BR, Evans BG. Use of blood culture vial specimens in intraoperative detection of
infection. Clin Orthop Relat Res 2001;(382):222-231.
Li DJ, Miles KA, Wraight EP. Bone scintigraphy of hip prostheses: Can analysis of
patterns of abnormality improve accuracy? Clinical Nuclear Medicine 1994;19(2):112115.
Lidwell OM, Lowbury EJ, Whyte W, Blowers R, Stanley SJ, Lowe D. Effect of
ultraclean air in operating rooms on deep sepsis in the joint after total hip or knee
replacement: a randomised study. Br Med J (Clin Res Ed) 1982;285(6334):10-14.
Lidwell OM, Lowbury EJ, Whyte W, Blowers R, Stanley SJ, Lowe D. Infection and
sepsis after operations for total hip or knee-joint replacement: influence of ultraclean air,
prophylactic antibiotics and other factors. J Hyg (Lond) 1984;93(3):505-529.
Lidwell OM, Elson RA, Lowbury EJ et al. Ultraclean air and antibiotics for prevention of
postoperative infection. A multicenter study of 8,052 joint replacement operations. Acta
Orthop Scand 1987;58(1):4-13.
Lieberman JR, Huo MH, Schneider R, Salvati EA, Rodi S. Evaluation of painful hip
arthroplasties. Are technetium bone scans necessary? J Bone Joint Surg Br
1993;75(3):475-478.
Lisowska B, Maslinski W, Maldyk P, Zabek J, Baranowska E. The role of cytokines in
inflammatory response after total knee arthroplasty in patients with rheumatoid arthritis.
Rheumatol Int 2008;28(7):667-671.
Logters T, Paunel-Gorgulu A, Zilkens C et al. Diagnostic accuracy of neutrophil-derived
circulating free DNA (cf-DNA/NETs) for septic arthritis. J Orthop Res 2009.
Lonner JH, Siliski JM, Scott RD. Prodromes of failure in total knee arthroplasty. J
Arthroplasty 1999;14(4):488-492.
Love C, Pugliese PV, Afriyie MO, Tomas MB, Marwin SE, Palestro CJ. 5. Utility of F18 FDG Imaging for Diagnosing the Infected Joint Replacement. Clin Positron Imaging
2000;3(4):159.
Love C, Tomas MB, Marwin SE, Pugliese PV, Palestro CJ. Role of nuclear medicine in
diagnosis of the infected joint replacement. Radiographics 2001;21(5):1229-1238.
Lubbeke A, Moons KG, Garavaglia G, Hoffmeyer P. Outcomes of obese and nonobese
patients undergoing revision total hip arthroplasty. Arthritis Rheum 2008;59(5):738-745.
253
v0.1 03.25.10
Lucht U. The Danish Hip Arthroplasty Register. Acta Orthop Scand 2000;71(5):433-439.
Lyons CW, Berquist TH, Lyons JC, Rand JA, Brown ML. Evaluation of radiographic
findings in painful hip arthroplasties. Clin Orthop Relat Res 1985;(195):239-251.
Mac HL, Reynolds MA, Treston-Aurand J, Henke JA. Comparison of autoreinfusion and
standard drainage systems in total joint arthroplasty patients. ORTHOP NURS
/19;12(3):19-25.
Maenpaa H, Laiho K, Kauppi M et al. A comparison of postoperative C-reactive protein
changes in primary and revision hip arthroplasty in patients with rheumatoid arthritis. J
Arthroplasty 2002;17(1):108-110.
Magyari Z, Fekete G, Molnar G. Diagnostic value of bone scintigraphy in the
complications of total replacement of the hip. Acta Chir Hung 1985;26(2):107-112.
Mahomed NN, Barrett JA, Katz JN et al. Rates and outcomes of primary and revision
total hip replacement in the United States medicare population. J Bone Joint Surg Am
2003;85-A(1):27-32.
Mahomed NN, Barrett J, Katz JN, Baron JA, Wright J, Losina E. Epidemiology of total
knee replacement in the United States Medicare population. J Bone Joint Surg Am
2005;87(6):1222-1228.
Malchau H, Herberts P, Ahnfelt L. Prognosis of total hip replacement in Sweden. Followup of 92,675 operations performed 1978-1990. Acta Orthop Scand 1993;64(5):497-506.
Malinzak RA, Ritter MA, Berend ME, Meding JB, Olberding EM, Davis KE. Morbidly
Obese, Diabetic, Younger, and Unilateral Joint Arthroplasty Patients Have Elevated Total
Joint Arthroplasty Infection Rates. J Arthroplasty 2009.
Mandalia V, Eyres K, Schranz P, Toms AD. Evaluation of patients with a painful total
knee replacement. J Bone Joint Surg Br 2008;90(3):265-271.
Mannien J, van Kasteren ME, Nagelkerke NJ et al. Effect of optimized antibiotic
prophylaxis on the incidence of surgical site infection. Infect Control Hosp Epidemiol
2006;27(12):1340-1346.
Mannien J, Wille JC, Snoeren RL, van den HS. Impact of postdischarge surveillance on
surgical site infection rates for several surgical procedures: results from the nosocomial
surveillance network in The Netherlands. Infect Control Hosp Epidemiol 2006;27(8):809816.
Mannien J, van den Hof S, Muilwijk J, van den Broek PJ, van BB, Wille JC. Trends in
the incidence of surgical site infection in the Netherlands. Infect Control Hosp Epidemiol
2008;29(12):1132-1138.
254
v0.1 03.25.10
Manthey N, Reinhard P, Moog F, Knesewitsch P, Hahn K, Tatsch K. The use of [18
F]fluorodeoxyglucose positron emission tomography to differentiate between synovitis,
loosening and infection of hip and knee prostheses. Nucl Med Commun 2002;23(7):645653.
Marchant MH, Jr., Viens NA, Cook C, Vail TP, Bolognesi MP. The impact of glycemic
control and diabetes mellitus on perioperative outcomes after total joint arthroplasty. J
Marculescu CE, Berbari EF, Hanssen AD, Steckelberg JM, Osmon DR. Prosthetic joint
infection diagnosed postoperatively by intraoperative culture. Clin Orthop Relat Res
2005;439:38-42.
Marculescu CE, Berbari EF, Cockerill FR, Osmon DR. Fungi, mycobacteria, zoonotic
and other organisms in prosthetic joint infection. Clinical orthopaedics and related
research 2006;-(451):64-72.
Marculescu CE, Berbari EF, Cockerill FR, Osmon DR. Unusual aerobic and anaerobic
bacteria associated with prosthetic joint infections. Clinical orthopaedics and related
research 2006;-(451):55-63.
Margaretten ME, Kohlwes J, Moore D, Bent S. Does this adult patient have septic
arthritis? JAMA 2007;297(13):1478-1488.
Mariani BD, Martin DS, Levine MJ, Booth RE, Jr., Tuan RS. The Coventry Award.
Polymerase chain reaction detection of bacterial infection in total knee arthroplasty. Clin
Orthop Relat Res 1996;(331):11-22.
Mariani BD, Martin DS, Levine MJ, Booth RE, Jr., Tuan RS. Polymerase chain reaction
detection of bacterial infection in total knee arthroplasty. Clinical orthopaedics and
related research 1996;-(331):11-22.
Marotte JH, Lord GA, Blanchard JP et al. Infection rate in total hip arthroplasty as a
function of air cleanliness and antibiotic prophylaxis. 10-year experience with 2,384
cementless Lord madreporic prostheses. J Arthroplasty 1987;2(1):77-82.
Mason JB, Fehring TK, Odum SM, Griffin WL, Nussman DS. The value of white blood
cell counts before revision total knee arthroplasty. J Arthroplasty 2003;18(8):1038-1043.
Maury CP, Teppo AM, Raunio P. Control of the acute-phase serum amyloid A and Creactive protein response: comparison of total replacement of the hip and knee. Eur J
Clin Invest 1984;14(5):323-328.
Maus TP, Berquist TH, Bender CE, Rand JA. Arthrographic study of painful total hip
arthroplasty: refined criteria. Radiology 1987;162(3):721-727.
McDonald DJ, Fitzgerald RH, Jr., Ilstrup DM. Two-stage reconstruction of a total hip
arthroplasty because of infection. J Bone Joint Surg Am 1989;71(6):828-834.
255
v0.1 03.25.10
McInerney DP, Hyde ID. Technetium 99Tcm pyrophosphate scanning in the assessment
of the painful hip prosthesis. Clin Radiol 1978;29(5):513-517.
McLaughlin JR, Lee KR. The outcome of total hip replacement in obese and non-obese
patients at 10- to 18-years. J Bone Joint Surg Br 2006;88(10):1286-1292.
McLaughlin RE, Whitehill R. Evaluation of the painful hip by aspiration and
arthrography. Surg Gynecol Obstet 1977;144(3):381-386.
McQueen M, Littlejohn A, Hughes SP. A comparison of systemic cefuroxime and
cefuroxime loaded bone cement in the prevention of early infection after total joint
replacement. Int Orthop 1987;11(3):241-243.
Meding JB, Reddleman K, Keating ME et al. Total Knee Replacement in Patients with
Diabetes Mellitus. Clinical orthopaedics and related research 2003;-(416):208-216.
Mehra A, Hemmady MV, Nelson R, Hodgkinson JP. Bacteriology swab in primary total
hip arthroplasty-- does it have a role? Int J Clin Pract 2006;60(6):665-666.
Menon TJ, Wroblewski BM. Charnley low-friction arthroplasty in patients with psoriasis.
Clin Orthop Relat Res 1983;(176):127-128.
Merkel KD, Brown ML, Dewanjee MK, Fitzgerald RH, Jr. Comparison of indiumlabeled-leukocyte imaging with sequential technetium-gallium scanning in the diagnosis
of low-grade musculoskeletal sepsis. A prospective study. J Bone Joint Surg Am
1985;67(3):465-476.
Merkel KD, Brown ML, Fitzgerald RH, Jr. Sequential technetium-99m HMDP-gallium67 citrate imaging for the evaluation of infection in the painful prosthesis. J Nucl Med
1986;27(9):1413-1417.
Mikkelsen DB, Pedersen C, Hojbjerg T, Schonheyder HC. Culture of multiple
peroperative biopsies and diagnosis of infected knee arthroplasties. APMIS
2006;114(6):449-452.
Miles KA, Harper WM, Finlay DB, Belton I. Scintigraphic abnormalities in patients with
painful hip replacements treated conservatively. Br J Radiol 1992;65(774):491-494.
Miner AL, Losina E, Katz JN, Fossel AH, Platt R. Deep infection after total knee
replacement: impact of laminar airflow systems and body exhaust suits in the modern
operating room. Infect Control Hosp Epidemiol 2007;28(2):222-226.
Mini E, Grassi F, Cherubino P, Nobili S, Periti P. Preliminary results of a survey of the
use of antimicrobial agents as prophylaxis in orthopedic surgery. J Chemother 2001;13
Spec No 1(1):73-79.
256
v0.1 03.25.10
Miniaci A, Bailey WH, Bourne RB, McLaren AC, Rorabeck CH. Analysis of
radionuclide arthrograms, radiographic arthrograms, and sequential plain radiographs in
the assessment of painful hip arthroplasty. J Arthroplasty 1990;5(2):143-149.
Minnema B, Vearncombe M, Augustin A, Gollish J, Simor AE. Risk factors for surgicalsite infection following primary total knee arthroplasty. Infect Control Hosp Epidemiol
2004;25(6):477-480.
Mirra JM, Amstutz HC, Matos M, Gold R. The pathology of the joint tissues and its
clinical relevance in prosthesis failure. Clin Orthop Relat Res 1976;(117):221-240.
Mirra JM, Marder RA, Amstutz HC. The pathology of failed total joint arthroplasty. Clin
Orthop Relat Res 1982;(170):175-183.
Mont MA, Mathur SK, Krackow KA, Loewy JW, Hungerford DS. Cementless total knee
arthroplasty in obese patients: A comparison with a matched control group. Journal of
Arthroplasty 1996;11(2):153-156.
Moojen DJ, Spijkers SN, Schot CS et al. Identification of orthopaedic infections using
broad-range polymerase chain reaction and reverse line blot hybridization. J Bone Joint
Surg Am 2007;89(6):1298-1305.
Mooney JF, III, Koman LA. Knee flexion contractures: soft tissue correction with
monolateral external fixation. J South Orthop Assoc 2001;10(1):32-36.
Moragas M, Lomena F, Herranz R et al. 99Tcm-HMPAO leucocyte scintigraphy in the
diagnosis of bone infection. Nucl Med Commun 1991;12(5):417-427.
Moran E, Masters S, Berendt AR, Lardy-Smith P, Byren I, Atkins BL. Guiding empirical
antibiotic therapy in orthopaedics: The microbiology of prosthetic joint infection
managed by debridement, irrigation and prosthesis retention. J Infect 2007;55(1):1-7.
Moran M, Walmsley P, Gray A, Brenkel IJ. Does body mass index affect the early
outcome of primary total hip arthroplasty? J Arthroplasty 2005;20(7):866-869.
Morawietz L, Tiddens O, Mueller M et al. Twenty-three neutrophil granulocytes in 10
high-power fields is the best histopathological threshold to differentiate between aseptic
and septic endoprosthesis loosening. Histopathology 2009;54(7):847-853.
Moreschini O, Greggi G, Giordano MC, Nocente M, Margheritini F. Postoperative
physiopathological analysis of inflammatory parameters in patients undergoing hip or
knee arthroplasty. Int J Tissue React 2001;23(4):151-154.
Mountford PJ, Hall FM, Wells CP, Coakley AJ. 99Tcm-MDP, 67Ga-citrate and 111Inleucocytes for detecting prosthetic hip infection. Nucl Med Commun 1986;7(2):113-120.
Moyad TF, Thornhill T, Estok D. Evaluation and management of the infected total hip
and knee. Orthopedics 2008;31(6):581-588.
257
v0.1 03.25.10
Muilwijk J, Walenkamp GH, Voss A, Wille JC, van den HS. Random effect modelling of
patient-related risk factors in orthopaedic procedures: results from the Dutch nosocomial
infection surveillance network 'PREZIES'. J Hosp Infect 2006;62(3):319-326.
Mulhall KJ, Ghomrawi HM, Scully S, Callaghan JJ, Saleh KJ. Current etiologies and
modes of failure in total knee arthroplasty revision. Clin Orthop Relat Res 2006;446:4550.
Mulier JC, Desmet L, Martens M, Hoogmartens M. Postoperative infection in total hip
replacement. Acta Orthop Belg 1973;39(3):630-643.
Muller M, Morawietz L, Hasart O, Strube P, Perka C, Tohtz S. Diagnosis of
periprosthetic infection following total hip arthroplasty - evaluation of the diagnostic
values of pre- and intraoperative parameters and the associated strategy to preoperatively
select patients with a high probability of joint infection. J Orthop Surg 2008;3:31.
Mumme T, Reinartz P, Alfer J, Muller-Rath R, Buell U, Wirtz DC. Diagnostic values of
positron emission tomography versus triple-phase bone scan in hip arthroplasty
loosening. Arch Orthop Trauma Surg 2005;125(5):322-329.
Murphy JP, Scott JE. The effectiveness of suction drainage in total hip arthroplasty.
Journal of the Royal Society of Medicine 1993;86(7):388-389.
Murray WR. Results in patients with total hip replacement arthroplasty. Clin Orthop
Relat Res 1973;(95):80-90.
Murray WR, Rodrigo JJ. Arthrography for the assessment of pain after total hip
replacement. A comparison of arthrographic findings in patients with and without pain. J
Musso AD, Mohanty K, Spencer-Jones R. Role of frozen section histology in diagnosis
of infection during revision arthroplasty. Postgrad Med J 2003;79(936):590-593.
Namba RS, Paxton L, Fithian DC, Stone ML. Obesity and perioperative morbidity in
total hip and total knee arthroplasty patients. J Arthroplasty 2005;20(7 Suppl 3):46-50.
Nelson CL, Evans RP, Blaha JD, Calhoun J, Henry SL, Patzakis MJ. A comparison of
gentamicin-impregnated polymethylmethacrylate bead implantation to conventional
parenteral antibiotic therapy in infected total hip and knee arthroplasty. Clin Orthop Relat
Res 1993;(295):96-101.
Nelson CL, Kim J, Lotke PA. Stiffness after total knee arthroplasty. Surgical technique.
J Bone Joint Surg Am 2005;87-A(Suppl 1 Pt 2):264-270.
Nelson JP, Glassburn AR, Jr., Talbott RD, McElhinney JP. The effect of previous
surgery, operating room environment, and preventive antibiotics on postoperative
infection following total hip arthroplasty. Clin Orthop Relat Res 1980;(147):167-169.
258
v0.1 03.25.10
Neut D, van H, Jr., van Kooten TG, van der Mei HC, Busscher HJ. Detection of
biomaterial-associated infections in orthopaedic joint implants. Clin Orthop Relat Res
2003;(413):261-268.
Niki Y, Matsumoto H, Otani T et al. Phenotypic characteristics of joint fluid cells from
patients with continuous joint effusion after total knee arthroplasty. Biomaterials
2006;27(8):1558-1565.
Niki Y, Matsumoto H, Otani T, Tomatsu T, Toyama Y. Five types of inflammatory
arthritis following total knee arthroplasty. J Biomed Mater Res A 2007;81(4):1005-1010.
Nilsdotter-Augustinsson A, Briheim G, Herder A, Ljunghusen O, Wahlstrom O, Ohman
L. Inflammatory response in 85 patients with loosened hip prostheses: a prospective
study comparing inflammatory markers in patients with aseptic and septic prosthetic
loosening. Acta Orthop 2007;78(5):629-639.
Niskanen RO, Korkala O, Pammo H. Serum C-reactive protein levels after total hip and
knee arthroplasty. J Bone Joint Surg Br 1996;78(3):431-433.
Nivbrant B, Karlsson K, Karrholm J. Cytokine levels in synovial fluid from hips with
well-functioning or loose prostheses. J Bone Joint Surg Br 1999;81(1):163-166.
Norden C, Nelson JD, Mader JT, Calandra GB. Evaluation of new anti-infective drugs
for the treatment of infections of prosthetic hip joints. Infectious Diseases Society of
America and the Food and Drug Administration. Clin Infect Dis 1992;15 Suppl 1:S177S181.
Norden CW. A critical review of antibiotic prophylaxis in orthopedic surgery. Rev Infect
Dis 1983;5(5):928-932.
O'Neill DA, Harris WH. Failed total hip replacement: assessment by plain radiographs,
arthrograms, and aspiration of the hip joint. J Bone Joint Surg Am 1984;66(4):540-546.
Okafor B, MacLellan G. Postoperative changes of erythrocyte sedimentation rate, plasma
viscosity and C-reactive protein levels after hip surgery. Acta Orthop Belg
1998;64(1):52-56.
Ong KL, Kurtz SM, Lau E, Bozic KJ, Berry DJ, Parvizi J. Prosthetic Joint Infection Risk
After Total Hip Arthroplasty in the Medicare Population. J Arthroplasty 2009.
Ouzounian TJ, Thompson L, Grogan TJ, Webber MM, Amstutz HC. Evaluation of
musculoskeletal sepsis with indium-111 white blood cell imaging. Clin Orthop Relat Res
1987;(221):304-311.
Oyen WJ, Claessens RA, van H, Jr., van der Meer JW, Corstens FH. Scintigraphic
detection of bone and joint infections with indium-111-labeled nonspecific polyclonal
human immunoglobulin G. J Nucl Med 1990;31(4):403-412.
259
v0.1 03.25.10
Oyen WJ, Claessens RA, van der Meer JW, Corstens FH. Detection of subacute
infectious foci with indium-111-labeled autologous leukocytes and indium-111-labeled
human nonspecific immunoglobulin G: a prospective comparative study. J Nucl Med
1991;32(10):1854-1860.
Oyen WJ, van H, Jr., Claessens RA, Slooff TJ, van der Meer JW, Corstens FH. Diagnosis
of bone, joint, and joint prosthesis infections with In-111-labeled nonspecific human
immunoglobulin G scintigraphy. Radiology 1992;182(1):195-199.
Paavolainen P, Hamalainen M, Mustonen H, Slatis P. Registration of arthroplasties in
Finland. A nationwide prospective project. Acta Orthop Scand Suppl 1991;241:27-30.
Padgett DE, Silverman A, Sachjowicz F, Simpson RB, Rosenberg AG, Galante JO.
Efficacy of intraoperative cultures obtained during revision total hip arthroplasty. J
Arthroplasty 1995;10(4):420-426.
Pakos EE, Trikalinos TA, Fotopoulos AD, Ioannidis JP. Prosthesis infection: diagnosis
after total joint arthroplasty with antigranulocyte scintigraphy with 99mTc-labeled
monoclonal antibodies--a meta-analysis. Radiology 2007;242(1):101-108.
Pakos EE, Fotopoulos AD, Stafilas KS et al. Use of (99m)Tc-sulesomab for the diagnosis
of prosthesis infection after total joint arthroplasty. J Int Med Res 2007;35(4):474-481.
Palermo F, Boccaletto F, Paolin A et al. Comparison of technetium-99m-MDP,
technetium-99m-WBC and technetium-99m-HIG in musculoskeletal inflammation. J
Nucl Med 1998;39(3):516-521.
Palestro CJ, Kim CK, Swyer AJ, Capozzi JD, Solomon RW, Goldsmith SJ. Total-hip
arthroplasty: periprosthetic indium-111-labeled leukocyte activity and complementary
technetium-99m-sulfur colloid imaging in suspected infection. J Nucl Med
1990;31(12):1950-1955.
Palestro CJ, Swyer AJ, Kim CK, Goldsmith SJ. Infected knee prosthesis: diagnosis with
In-111 leukocyte, Tc-99m sulfur colloid, and Tc-99m MDP imaging. Radiology
1991;179(3):645-648.
Palestro CJ, Roumanas P, Swyer AJ, Kim CK, Goldsmith SJ. Diagnosis of
musculoskeletal infection using combined In-111 labeled leukocyte and Tc-99m SC
marrow imaging. Clin Nucl Med 1992;17(4):269-273.
Pandey R, Drakoulakis E, Athanasou NA. An assessment of the histological criteria used
to diagnose infection in hip revision arthroplasty tissues. J Clin Pathol 1999;52(2):118123.
Pandey R, Berendt AR, Athanasou NA. Histological and microbiological findings in noninfected and infected revision arthroplasty tissues. The OSIRIS Collaborative Study
Group. Oxford Skeletal Infection Research and Intervention Service. Arch Orthop
Trauma Surg 2000;120(10):570-574.
260
v0.1 03.25.10
Pandey R, Berendt AR, Athanasou NA. Histological and microbiological findings in noninfected and infected revision arthroplasty tissues. Archives of Orthopaedic and Trauma
Surgery 2000;120(10):570-574.
Panousis K, Grigoris P, Butcher I, Rana B, Reilly JH, Hamblen DL. Poor predictive value
of broad-range PCR for the detection of arthroplasty infection in 92 cases. Acta Orthop
2005;76(3):341-346.
Papagelopoulos PJ, Idusuyi OB, Wallrichs SL, Morrey BF. Long term outcome and
survivorship analysis of primary total knee arthroplasty in patients with diabetes mellitus.
Clin Orthop Relat Res 1996;(330):124-132.
Park KK, Kim TK, Chang CB, Yoon SW, Park KU. Normative Temporal Values of CRP
and ESR in Unilateral and Staged Bilateral TKA. Clin Orthop Relat Res
2008;466(1):179-188.
Parker MJ, Roberts CP, Hay D. Closed suction drainage for hip and knee arthroplasty. A
meta-analysis. J Bone Joint Surg Am 2004;86-A(6):1146-1152.
Parker MJ, Livingstone V, Clifton R, McKee A. Closed suction surgical wound drainage
after orthopaedic surgery. Cochrane Database Syst Rev 2007;(3):CD001825.
Parratte S, Pagnano MW. The Stiff Total Knee Arthroplasty: A Contemporary Approach.
Seminars in Arthroplasty 2008;19(1):98-102.
Partanen J, Syrjala H, Vahanikkila H, Jalovaara P. Impact of deep infection after hip
fracture surgery on function and mortality. J Hosp Infect 2006;62(1):44-49.
Partio E, Orava T, Lehto MU, Lindholm ST. Survival of the Townley knee. 360 cases
with 8 (0.1-15) years' follow-up. Acta Orthop Scand 1994;65(3):319-322.
Parvizi J, Tarity TD, Steinbeck MJ et al. Management of stiffness following total knee
arthroplasty. J Bone Joint Surg Am 2006;88 Suppl 4:175-181.
Parvizi J, Ghanem E, Joshi A, Sharkey PF, Hozack WJ, Rothman RH. Does "excessive"
anticoagulation predispose to periprosthetic infection? J Arthroplasty 2007;22(6 Suppl
2):24-28.
Parvizi J, Saleh KJ, Ragland PS, Pour AE, Mont MA. Efficacy of antibiotic-impregnated
cement in total hip replacement. Acta Orthop 2008;79(3):335-341.
Pasticci MB, Mancini G, Lapalorcia LM et al. Prosthetic infections following total knee
arthroplasty: A six-year prospective study (1997-2002). Journal of Orthopaedics and
Traumatology 2007;8(1):25-28.
Patel VP, Walsh M, Sehgal B, Preston C, DeWal H, Di Cesare PE. Factors associated
with prolonged wound drainage after primary total hip and knee arthroplasty. J Bone
Joint Surg Am 2007;89(1):33-38.
261
v0.1 03.25.10
Pearlman AW. The painful hip prosthesis: value of nuclear imaging in the diagnosis of
late complications. Clin Nucl Med 1980;5(4):133-142.
Peersman G, Laskin R, Davis J, Peterson MG, Richart T. Prolonged operative time
correlates with increased infection rate after total knee arthroplasty. HSS J 2006;2(1):7072.
Peersman G, Laskin R, Davis J, Peterson MG, Richart T. ASA physical status
classification is not a good predictor of infection for total knee replacement and is
influenced by the presence of comorbidities. Acta Orthop Belg 2008;74(3):360-364.
Pelosi E, Baiocco C, Pennone M et al. 99mTc-HMPAO-leukocyte scintigraphy in
patients with symptomatic total hip or knee arthroplasty: improved diagnostic accuracy
by means of semiquantitative evaluation. J Nucl Med 2004;45(3):438-444.
Perdreau-Remington F, Stefanik D, Peters G et al. A four-year prospective study on
microbial ecology of explanted prosthetic hips in 52 patients with "aseptic" prosthetic
joint loosening. Eur J Clin Microbiol Infect Dis 1996;15(2):160-165.
Perka C, Labs K, Muschik M, Buttgereit F. The influence of obesity on perioperative
morbidity and mortality in revision total hip arthroplasty. Arch Orthop Trauma Surg
2000;120(5-6):267-271.
Petty W, Bryan RS, Coventry MB, Peterson LF. Infection after total knee arthroplasty.
Orthop Clin North Am 1975;6(4):1005-1014.
Phillips CB, Barrett JA, Losina E et al. Incidence rates of dislocation, pulmonary
embolism, and deep infection during the first six months after elective total hip
replacement. J Bone Joint Surg Am 2003;85-A(1):20-26.
Phillips JE, Crane TP, Noy M, Elliott TS, Grimer RJ. The incidence of deep prosthetic
infections in a specialist orthopaedic hospital: a 15-year prospective survey. J Bone Joint
Surg Br 2006;88(7):943-948.
Phillips WC, Kattapuram SV. Efficacy of preoperative hip aspiration performed in the
radiology department. Clin Orthop Relat Res 1983;(179):141-146.
Picado CH, Garcia FL, Chagas MV, Jr., Toquetao FG. Accuracy of intraoperative
cultures in primary total hip arthroplasty. Hip Int 2008;18(1):46-50.
Pipino F, Molfetta L, Resta L, Facilone A, Brandonisio O, Altamura M. Bacteriological
and histological study of 40 loose cemented hip prostheses. Ital J Orthop Traumatol
1989;15(4):481-490.
Pizzoferrato A, Fiori F, Savarino L. Microbiological investigation of 161 cases of hip
endo-arthroprosthesis failure. Chir Organi Mov 1980;66(3):297-307.
262
v0.1 03.25.10
Poss R, Thornhill TS, Ewald FC, Thomas WH, Batte NJ, Sledge CB. Factors influencing
the incidence and outcome of infection following total joint arthroplasty. Clin Orthop
Relat Res 1984;(182):117-126.
Prchal CL, Kahen HL, Blend MJ, Barmada R. Detection of musculoskeletal infection
with the indium-III leukocyte scan. Orthopedics 1987;10(9):1253-1257.
Pring DJ, Henderson RG, Keshavarzian A et al. Indium-granulocyte scanning in the
painful prosthetic joint. AJR Am J Roentgenol 1986;147(1):167-172.
Pritchett JW, Bortel DT. Knee replacement in morbidly obese women. Surg Gynecol
Obstet 1991;173(2):119-122.
Puolakka TJ, Pajamaki KJ, Halonen PJ, Pulkkinen PO, Paavolainen P, Nevalainen JK.
The Finnish Arthroplasty Register: report of the hip register. Acta Orthop Scand
2001;72(5):433-441.
Ragni MV, Crossett LS, Herndon JH. Postoperative infection following orthopaedic
surgery in human immunodeficiency virus-infected hemophiliacs with CD4 counts (lessthan or equal to) 200/mm(3). Journal of Arthroplasty 1995;10(6):716-721.
Reilly J, Allardice G, Bruce J, Hill R, McCoubrey J. Procedure-specific surgical site
infection rates and postdischarge surveillance in Scotland. Infect Control Hosp Epidemiol
2006;27(12):1318-1323.
Reinartz P, Mumme T, Hermanns B et al. Radionuclide imaging of the painful hip
arthroplasty: positron-emission tomography versus triple-phase bone scanning. J Bone
Joint Surg Br 2005;87(4):465-470.
Reinartz P, Mumme T, Hermanns B et al. Radionuclide imaging of the painful hip
arthroplasty. Journal of Bone and Joint Surgery - Series B 2005;87(4):465-470.
Reinus WR, Merkel KC, Gilden JJ, Berger KL. Evaluation of femoral prosthetic
loosening using CT imaging. AJR Am J Roentgenol 1996;166(6):1439-1442.
Reuland P, Winker KH, Heuchert T et al. Detection of infection in postoperative
orthopedic patients with technetium-99m-labeled monoclonal antibodies against
granulocytes. J Nucl Med 1991;32(12):2209-2214.
Ridgeway S, Wilson J, Charlet A, Kafatos G, Pearson A, Coello R. Infection of the
surgical site after arthroplasty of the hip. J Bone Joint Surg Br 2005;87(6):844-850.
Ringberg H, Sanzen L, Thoren A, Walder M. Bacteriologic evidence of infection caused
by coagulase-negative staphylococci in total hip replacement. J Arthroplasty
1998;13(8):935-938.
263
v0.1 03.25.10
Robbins GM, Masri BA, Garbuz DS, Duncan CP. Evaluation of pain in patients with
apparently solidly fixed total hip arthroplasty components. J Am Acad Orthop Surg
2002;10(2):86-94.
Roberts P, Walters AJ, McMinn DJ. Diagnosing infection in hip replacements. The use of
fine-needle aspiration and radiometric culture. J Bone Joint Surg Br 1992;74(2):265-269.
Robertsson O, Borgquist L, Knutson K, Lewold S, Lidgren L. Use of unicompartmental
instead of tricompartmental prostheses for unicompartmental arthrosis in the knee is a
cost-effective alternative. 15,437 primary tricompartmental prostheses were compared
with 10,624 primary medial or lateral unicompartmental prostheses. Acta Orthop Scand
1999;70(2):170-175.
Rodriguez-Merchan EC. Total knee replacement in haemophilic arthropathy. J Bone
Joint Surg Br 2007;89(2):186-188.
Rosas MH, Leclercq S, Pegoix M et al. Contribution of laboratory tests, scintigraphy, and
histology to the diagnosis of lower limb joint replacement infection. Rev Rhum Engl Ed
1998;65(7-9):477-482.
Rubello D, Borsato N, Chierichetti F, Zanco P, Ferlin G. Three-phase bone scintigraphy
pattern of loosening in uncemented hip prostheses. Eur J Nucl Med 1995;22(4):299-301.
Rubello D, Casara D, Maran A, Avogaro A, Tiengo A, Muzzio PC. Role of antigranulocyte Fab' fragment antibody scintigraphy (LeukoScan) in evaluating bone
infection: acquisition protocol, interpretation criteria and clinical results. Nucl Med
Commun 2004;25(1):39-47.
Rubello D, Rampin L, Banti E et al. Diagnosis of infected total knee arthroplasty with
anti-granulocyte scintigraphy: the importance of a dual-time acquisition protocol. Nucl
Med Commun 2008;29(4):331-335.
Rubin RH, Fischman AJ, Callahan RJ et al. 111In-labeled nonspecific immunoglobulin
scanning in the detection of focal infection. N Engl J Med 1989;321(14):935-940.
Rushton N, Coakley AJ, Tudor J, Wraight EP. The value of technetium and gallium
scanning in assessing pain after total hip replacement. J Bone Joint Surg Br
1982;64(3):313-318.
Ryan PJ. Leukoscan for orthopaedic imaging in clinical practice. Nucl Med Commun
2002;23(8):707-714.
Sachs RA, Smith JH, Kuney M, Paxton L. Does anticoagulation do more harm than
good?: A comparison of patients treated without prophylaxis and patients treated with
low-dose warfarin after total knee arthroplasty. J Arthroplasty 2003;18(4):389-395.
Sadiq S, Wootton JR, Morris CA, Northmore-Ball MD. Application of core biopsy in
revision arthroplasty for deep infection. J Arthroplasty 2005;20(2):196-201.
264
v0.1 03.25.10
Sadr AO, Bellocco R, Eriksson K, Adami J. The impact of tobacco use and body mass
index on the length of stay in hospital and the risk of post-operative complications among
patients undergoing total hip replacement. J Bone Joint Surg Br 2006;88(10):1316-1320.
Salenius P, Vankka E. Arthrography of the hip in the diagnosis of postoperative painful
conditions after total hip replacement. Annales chirurgiae et gynaecologiae
1979;68(4):121-126.
Salvati EA, Freiberger RH, Wilson PD, Jr. Arthrography for complications of total hip
replacement. A review of thirty-one arthrograms. J Bone Joint Surg Am 1971;53(4):701709.
Sanzen L. The erythrocyte sedimentation rate following exchange of infected total hips.
Acta Orthop Scand 1988;59(2):148-150.
Sanzen L, Carlsson AS. The diagnostic value of C-reactive protein in infected total hip
arthroplasties. J Bone Joint Surg Br 1989;71(4):638-641.
Sanzen L, Sundberg M. Periprosthetic low-grade hip infections. Erythrocyte
sedimentation rate and C-reactive protein in 23 cases. Acta Orthop Scand
1997;68(5):461-465.
Savarino L, Tigani D, Baldini N, Bochicchio V, Giunti A. Pre-operative diagnosis of
infection in total knee arthroplasty: an algorithm. Knee Surg Sports Traumatol Arthrosc
2009;17(6):667-675.
Sayle BA, Fawcett HD, Wilkey DJ, Cierny G, III, Mader JT. Indium-111 chloride
imaging in the detection of infected prostheses. J Nucl Med 1985;26(7):718-721.
Schmalzried TP, Amstutz HC, Au MK, Dorey FJ. Incidence of deep sepsis in total hip
arthroplasty. Survivorship analysis over 17 years from one hospital. J Arthroplasty
1991;6 Suppl:S47-S51.
Schmalzried TP, Amstutz HC, Au MK, Dorey FJ. Etiology of deep sepsis in total hip
arthroplasty. The significance of hematogenous and recurrent infections. Clin Orthop
Relat Res 1992;(280):200-207.
Schneider R, Freiberger RH, Ghelman B, Ranawat CS. Radiologic evaluation of painful
joint prostheses. Clin Orthop Relat Res 1982;(170):156-168.
Schulak DJ, Rayhack JM, Lippert FG, III, Convery FR. The erythrocyte sedimentation
rate in orthopaedic patients. Clin Orthop Relat Res 1982;(167):197-202.
Schulitz KP, Winkelmann W, Schoening B. The prophylactic use of antibiotics in
alloarthroplasty of the hip joint for coxarthrosis. A randomized study. ARCH ORTHOP
TRAUM SURG 1980;96:79-82.
265
v0.1 03.25.10
Schwenger V, Sis J, Breitbart A, Andrassy K. CRP levels in autoimmune disease can be
specified by measurement of procalcitonin. Infection 1998;26(5):274-276.
Sciuk J, Puskas C, Greitemann B, Schober O. White blood cell scintigraphy with
monoclonal antibodies in the study of the infected endoprosthesis. Eur J Nucl Med
1992;19(7):497-502.
Scuderi GR. The stiff total knee arthroplasty: Causality and solution. Journal of
Arthroplasty 2005;20(SUPPL. 2):23-26.
Serna F, Mont MA, Krackow KA, Hungerford DS. Total knee arthroplasty in diabetic
patients. Comparison to a matched control group. J Arthroplasty 1994;9(4):375-379.
Sfakianakis GN, Al-Sheikh W, Heal A, Rodman G, Zeppa R, Serafini A. Comparisons of
scintigraphy with In-111 leukocytes and Ga-67 in the diagnosis of occult sepsis. J Nucl
Med 1982;23(7):618-626.
Shih L-Y, Wu J-J, Yang D-J. Erythrocyte sedimentation rate and C-reactive protein
values in patients with total hip arthroplasty. Clinical orthopaedics and related research
1987;-(225):238-246.
Shih LY, Cheng CY, Chang CH, Hsu KY, Hsu RW, Shih HN. Total knee arthroplasty in
patients with liver cirrhosis. J Bone Joint Surg Am 2004;86-A(2):335-341.
Shrader MW, Morrey BF. Primary TKA in Patients with Lymphedema. Clinical
orthopaedics and related research 2003;-(416):22-26.
Sierra RJ, Cooney WP, Pagnano MW, Trousdale RT, Rand JA. Reoperations after 3200
revision TKAs: rates, etiology, and lessons learned. Clin Orthop Relat Res
2004;(425):200-206.
Silva M, Luck JV, Jr. Long-term results of primary total knee replacement in patients
with hemophilia. J Bone Joint Surg Am 2005;87(1):85-91.
Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J. Serum procalcitonin and Creactive protein levels as markers of bacterial infection: a systematic review and metaanalysis. Clin Infect Dis 2004;39(2):206-217.
Simonsen L, Buhl A, Oersnes T, Duus B. White blood cell scintigraphy for
differentiation of infection and aseptic loosening: a retrospective study of 76 painful hip
prostheses. Acta Orthop 2007;78(5):640-647.
Smith SL, Wastie ML, Forster I. Radionuclide bone scintigraphy in the detection of
significant complications after total knee joint replacement. Clin Radiol 2001;56(3):221224.
Sofka CM, Potter HG, Figgie M, Laskin R. Magnetic resonance imaging of total knee
266
v0.1 03.25.10
Solomon DH, Chibnik LB, Losina E et al. Development of a preliminary index that
predicts adverse events after total knee replacement. Arthritis Rheum 2006;54(5):15361542.
Somme D, Ziza JM, Desplaces N et al. Contribution of routine joint aspiration to the
diagnosis of infection before hip revision surgery. Joint Bone Spine 2003;70(6):489-495.
Spangehl MJ, Younger ASE, Masri BA, Duncan CP. Diagnosis of infection following
total hip arthroplasty. Journal of Bone and Joint Surgery - Series A 1997;79(10):15781588.
Spicer DD, Pomeroy DL, Badenhausen WE et al. Body mass index as a predictor of
outcome in total knee replacement. Int Orthop 2001;25(4):246-249.
Spinelli R. The role of scintigraphy in the diagnosis of late complications of total
prosthesis of the hip. (Infection, loosening, ossification). Ital J Orthop Traumatol
1976;2(1):79-87.
Steinbach LS, Schneider R, Goldman AB, Kazam E, Ranawat CS, Ghelman B. Bursae
and abscess cavities communicating with the hip. Diagnosis using arthrography and CT.
Radiology 1985;156(2):303-307.
Stern SH, Insall JN, Windsor RE, Inglis AE, Dines DM. Total knee arthroplasty in
patients with psoriasis. Clin Orthop Relat Res 1989;(248):108-110.
Stern SH, Insall JN. Total knee arthroplasty in obese patients. J Bone Joint Surg Am
1990;72(9):1400-1404.
Streule K, de SM, Fridrich R. 99Tcm-labelled HSA-nanocolloid versus 111In oxinelabelled granulocytes in detecting skeletal septic process. Nucl Med Commun
1988;9(1):59-67.
Stumpe KD, Notzli HP, Zanetti M et al. FDG PET for differentiation of infection and
aseptic loosening in total hip replacements: comparison with conventional radiography
and three-phase bone scintigraphy. Radiology 2004;231(2):333-341.
Stumpe KD, Romero J, Ziegler O et al. The value of FDG-PET in patients with painful
total knee arthroplasty. Eur J Nucl Med Mol Imaging 2006;33(10):1218-1225.
Surin VV, Sundholm K, Backman L. Infection after total hip replacement. With special
reference to a discharge from the wound. J Bone Joint Surg Br 1983;65(4):412-418.
Syahrizal AB, Kareem BA, Anbanadan S, Harwant S. Risk factors for infection in total
knee replacement surgery at hospital Kuala Lumpur. Med J Malaysia 2001;56 Suppl
D:5-8.
267
v0.1 03.25.10
Szilagyi E, Borocz K, Gastmeier P, Kurcz A, Horvath-Puho E. The national nosocomial
surveillance network in Hungary: results of two years of surgical site infection
surveillance. J Hosp Infect 2008.
Tannenbaum DA, Matthews LS, Grady-Benson JC. Infection around joint replacements
in patients who have a renal or liver transplantation. Journal of Bone and Joint Surgery Series A 1997;79(1):36-43.
Taylor DN, Maughan J, Patel MP, Clegg J. A simple method of identifying loosening or
infection of hip prostheses in nuclear medicine. Nucl Med Commun 1989;10(8):551-556.
Taylor T, Beggs I. Fine needle aspiration in infected hip replacements. Clin Radiol
1995;50(3):149-152.
Tehranzadeh J, Schneider R, Freiberger RH. Radiological evaluation of painful total hip
replacement. Radiology 1981;141(2):355-362.
Thomas C, Cadwallader HL, Riley TV. Surgical-site infections after orthopaedic surgery:
statewide surveillance using linked administrative databases. J Hosp Infect
2004;57(1):25-30.
Thoren B, Wigren A. Erythrocyte sedimentation rate in infection of total hip
replacements. Orthopedics 1991;14(4):495-497.
Tietjen R, Stinchfield FE, Michelsen CB. The significance of intracapsular cultures in
total hip operations. Surg Gynecol Obstet 1977;144(5):699-702.
Tigges S, Stiles RG, Meli RJ, Roberson JR. Hip aspiration: a cost-effective and accurate
method of evaluating the potentially infected hip prosthesis. Radiology 1993;189(2):485488.
Tsukayama DT, Estrada R, Gustilo RB. Infection after total hip arthroplasty. A study of
the treatment of one hundred and six infections. J Bone Joint Surg Am 1996;78(4):512523.
Tunney MM, Patrick S, Gorman SP et al. Improved detection of infection in hip
replacements. A currently underestimated problem. J Bone Joint Surg Br 1998;80(4):568572.
Tunney MM, Patrick S, Gorman SP et al. Improved detection of infection in hip
replacements. Journal of Bone and Joint Surgery - Series B 1998;80(4):568-572.
Tunney MM, Patrick S, Curran MD et al. Detection of prosthetic joint biofilm infection
using immunological and molecular techniques. Methods Enzymol 1999;310:566-576.
Tunney MM, Patrick S, Curran MD et al. Detection of prosthetic hip infection at revision
arthroplasty by immunofluorescence microscopy and PCR amplification of the bacterial
16S rRNA gene. J Clin Microbiol 1999;37(10):3281-3290.
268
v0.1 03.25.10
Uzzan B, Cohen R, Nicolas P, Cucherat M, Perret GY. Procalcitonin as a diagnostic test
for sepsis in critically ill adults and after surgery or trauma: a systematic review and
meta-analysis. Crit Care Med 2006;34(7):1996-2003.
Van den Bekerom MP, Stuyck J. The value of pre-operative aspiration in the diagnosis of
an infected prosthetic knee: a retrospective study and review of literature. Acta Orthop
Belg 2006;72(4):441-447.
van Holsbeeck MT, Eyler WR, Sherman LS et al. Detection of infection in loosened hip
prostheses: efficacy of sonography. AJR Am J Roentgenol 1994;163(2):381-384.
Van Kasteren MEE, Mannien J, Ott A, Kullberg B-J, de Boer AS, Gyssens IC. Antibiotic
prophylaxis and the risk of surgical site infections following total hip arthroplasty:
Timely administration is the most important factor. Clinical Infectious Diseases
2007;44(7):921-927.
van Loon CJ, Wisse MA, de Waal Malefijt MC, Jansen RH, Veth RP. The kinematic total
knee arthroplasty. A 10- to 15-year follow-up and survival analysis. Arch Orthop Trauma
Surg 2000;120(1-2):48-52.
Van AF, Nuyts J, Maes A et al. FDG-PET, 99mtc-HMPAO white blood cell SPET and
bone scintigraphy in the evaluation of painful total knee arthroplasties. Eur J Nucl Med
2001;28(10):1496-1504.
Vannini P, Ciavarella A, Olmi R et al. Diabetes as pro-infective risk factor in total hip
replacement. Acta Diabetol Lat 1984;21(3):275-280.
Vanquickenborne B, Maes A, Nuyts J et al. The value of (18)FDG-PET for the detection
of infected hip prosthesis. Eur J Nucl Med Mol Imaging 2003;30(5):705-715.
Varley GW, Milner SA. Wound drains in proximal femoral fracture surgery: a
randomized prospective trial of 177 patients. J R Coll Surg Edinb 1995;40(6):416-418.
Vicente AG, Almoguera M, Alonso JC et al. Diagnosis of orthopedic infection in clinical
practice using Tc-99m sulesomab (antigranulocyte monoclonal antibody fragment Fab'2).
Clin Nucl Med 2004;29(12):781-785.
Vinjamuri S, Hall AV, Solanki KK et al. Comparison of 99mTc infecton imaging with
radiolabelled white-cell imaging in the evaluation of bacterial infection. Lancet
1996;347(8996):233-235.
Virolainen P, Lahteenmaki H, Hiltunen A, Sipola E, Meurman O, Nelimarkka O. The
reliability of diagnosis of infection during revision arthroplasties. Scand J Surg
2002;91(2):178-181.
von RT, Schoellhammer M, Schaffstein J, Koester O, Schmid G. Imaging of infected
total arthroplasty with Tc-99m-labeled antigranulocyte antibody Fab'fragments. Clin Nucl
Med 2004;29(9):548-551.
269
v0.1 03.25.10
Waldman BJ, Mont MA, Hungerford DS. Total knee arthroplasty infections associated
with dental procedures. Clin Orthop Relat Res 1997;(343):164-172.
Walker CW, FitzRandolph RL, Collins DN, Dalrymple GV. Arthrography of painful hips
following arthroplasty: digital versus plain film subtraction. Skeletal Radiol
1991;20(6):403-407.
Wang WN. Clinical observations on Blauth's total endoprosthesis of the knee joint. Arch
Orthop Trauma Surg 1984;103(4):263-268.
Weidenhielm LRA, Mikhail WEM, Wretenberg P, Fow J, Simpson J, Bauer TW.
Analysis of the retrieved hip after revision with impaction grafting. Acta orthopaedica
Scandinavica 2001;72(6):609-614.
Weiss AP, Krackow KA. Persistent wound drainage after primary total knee arthroplasty.
J Arthroplasty 1993;8(3):285-289.
Weiss PE, Mall JC, Hoffer PB, Murray WR, Rodrigo JJ, Genant HK. 99mTc-methylene
diphosphonate bone imaging in the evaluation of total hip prostheses. Radiology
1979;133(3 Pt 1):727-729.
Wellman HN, Schauwecker DS, Capello WN. Evaluation of metallic osseous implants
with nuclear medicine. Semin Nucl Med 1988;18(2):126-136.
Went P, Krismer M, Frischhut B. Recurrence of infection after revision of infected hip
arthroplasties. J Bone Joint Surg Br 1995;77(2):307-309.
White J, Kelly M, Dunsmuir R. C-reactive protein level after total hip and total knee
replacement. J Bone Joint Surg Br 1998;80(5):909-911.
White RH, McCurdy SA, Marder RA. Early morbidity after total hip replacement:
rheumatoid arthritis versus osteoarthritis. J Gen Intern Med 1990;5(4):304-309.
Williams ED, Tregonning RJ, Hurley PJ. 99Tcm-diphosphonate scanning as an aid to
diagnosis of infection in total hip joint replacements. Br J Radiol 1977;50(596):562-566.
Williams F, McCall IW, Park WM, O'Connor BT, Morris V. Gallium-67 scanning in the
painful total hip replacement. Clin Radiol 1981;32(4):431-439.
Wilson J, Charlett A, Leong G, McDougall C, Duckworth G. Rates of surgical site
infection after hip replacement as a hospital performance indicator: analysis of data from
the English mandatory surveillance system. Infect Control Hosp Epidemiol
2008;29(3):219-226.
Wilson MG, Kelley K, Thornhill TS. Infection as a complication of total kneereplacement arthroplasty. Risk factors and treatment in sixty-seven cases. J Bone Joint
Surg Am 1990;72(6):878-883.
270
v0.1 03.25.10
Winiarsky R, Barth P, Lotke P. Total knee arthroplasty in morbidly obese patients. J
Wolf G, Aigner RM, Schwarz T, Lorbach MP. Localization and diagnosis of septic
endoprosthesis infection by using 99mTc-HMPAO labelled leucocytes. Nucl Med
Commun 2003;24(1):23-28.
Wong YC, Lee QJ, Wai YL, Ng WF. Intraoperative frozen section for detecting active
infection in failed hip and knee arthroplasties. J Arthroplasty 2005;20(8):1015-1020.
Wukich DK, Abreu SH, Callaghan JJ et al. Diagnosis of infection by preoperative
scintigraphy with indium-labeled white blood cells. J Bone Joint Surg Am
1987;69(9):1353-1360.
Yapar Z, Kibar M, Yapar AF, Togrul E, Kayaselcuk U, Sarpel Y. The efficacy of
technetium-99m ciprofloxacin (Infecton) imaging in suspected orthopaedic infection: a
comparison with sequential bone/gallium imaging. Eur J Nucl Med 2001;28(7):822-830.
Yasunaga H, Tsuchiya K, Matsuyama Y, Ohe K. High-volume surgeons in regard to
reductions in operating time, blood loss, and postoperative complications for total hip
arthroplasty. Journal of Orthopaedic Science 2009;14(1):3-9.
Yasunaga H, Tsuchiya K, Matsuyama Y, Ohe K. Analysis of factors affecting operating
time, postoperative complications, and length of stay for total knee arthroplasty:
Nationwide web-based survey. Journal of Orthopaedic Science 2009;14(1):10-16.
Yong KS, Kareem BA, Ruslan GN, Harwant S. Risk factors for infection in total hip
replacement surgery at Hospital Kuala Lumpur. Med J Malaysia 2001;56 Suppl C:57-60.
Zamora-Navas P, Collado-Torres F, de lT-S. Closed suction drainage after knee
arthroplasty. A prospective study of the effectiveness of the operation and of bacterial
contamination. Acta Orthop Belg 1999;65(1):44-47.
Zhan C, Kaczmarek R, Loyo-Berrios N, Sangl J, Bright RA. Incidence and short-term
outcomes of primary and revision hip replacement in the United States. J Bone Joint Surg
Am 2007;89(3):526-533.
Zhuang H, Duarte PS, Pourdehnad M et al. The promising role of 18F-FDG PET in
detecting infected lower limb prosthesis implants. J Nucl Med 2001;42(1):44-48.
Zhuang H, Chacko TK, Hickeson M et al. Persistent non-specific FDG uptake on PET
imaging following hip arthroplasty. Eur J Nucl Med Mol Imaging 2002;29(10):13281333.
Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint infections. N Engl J Med
2004;351(16):1645-1654.
271
v0.1 03.25.10
Zoccali C, Teori G, Salducca N. The role of FDG-PET in distinguishing between septic
and aseptic loosening in hip prosthesis: a review of literature. Int Orthop 2008.
272
v0.1 03.25.10

File - Working Toward Zero HAIs

Transcription

Similar documents

Brandon Broome, MD, Steadman Hawkins Clinic of the Carolinas

Makoplasty Brochure

hip hOp - Groupe Lacasse

The Best Butt Workout PDF

View Current Brochure - NovaCare Rehabilitation

7pm Where

suggestions from the field Four-Bar Gait-Control Linkage

leeloo bandage costume

See full Boigraphy of thabzero

15 Minutes to a Better Body